Ophthalmic Artery Flow Pattern-related Stump Pressure and Ischemic Tolerance during Balloon Test Occlusion of the Internal Carotid Artery

Very few studies have described the blood flow pattern in the ipsilateral ophthalmic artery (OphA) during internal carotid artery (ICA) balloon test occlusion performed to estimate the risk of cerebral ischemia associated with therapeutic ICA sacrifice. This study aimed to investigate the relationship between ipsilateral OphA flow patterns just after ICA temporary occlusion and balloon test occlusion findings. We retrospectively reviewed 32 balloon test occlusion procedures performed at our institution between 2010 and 2019, and analyzed the OphA flow patterns and the conventional balloon test occlusion assessment items: neurological symptoms, stump pressure, stump-pressure ratio, collateral circulations, and venous phase delay. The flow patterns were categorized as type I (retrograde flow reaching the middle cerebral artery [MCA]), type II (retrograde flow to the ICA not reaching the MCA), or type III (no retrograde flow). Tolerance to balloon test occlusion was observed in 4/21 patients (19.0%), 4/6 patients (66.7%), and all five patients with types I, II, and III flows, respectively. The mean pressure ratios during balloon test occlusion in flow types I, II, and III were 35.6% ± 3.5%, 56.4% ± 6.5%, and 69.4% ± 7.1%, respectively (P <0.001). The mean stump pressures in flow types I, II, and III were 36.2 ± 3.6 mmHg, 46.6 ± 6.7 mmHg, and 66.6 ± 7.3 mmHg, respectively (P = 0.003). The mean venous phase delay in flow types I, II, and III were 0.99 ± 0.14 s, 0.25 ± 0.25 s, and 0.0 ± 0.28 s, respectively (P = 0.004). All the above variables showed significant flow-related differences. These results suggest that the OphA flow patterns may provide an additional diagnostic criterion for balloon test occlusion.     

A sighted man with non-24-hour sleep-wake syndrome shows damped plasma melatonin rhythm

Abstract Twenty-four-hour profiles of plasma melatonin, cortisol and rectal temperature were measured longitudinally in a sighted man who has been suffering from sleep disorders for more than 10 years. The sleep-wake rhythm of this subject free-ran, despite his routine life, and occasionally showed a sign of internal desyn-chronization, where sleep was lengthened up to 30 h. These states were classified into the non-24-hour sleep-wake syndrome. Plasma melatonin concentrations in the subjective night remained at a low level and showed a damped circadian rhythm. At the same time, robust circadian rhythms were detected in plasma cortisol and rectal temperature, indicating that the circadian pacemaker was intact. The causal relationship between the damping of nocturnal melatonin rise and a failure of entrainment of the sleep-wake cycle is discussed.     

Long-term effect of α-glucosidase inhibitor on late dumping syndrome

Dumping syndrome commonly occurs after gastrectomy. The late dumping, which is one of the dumping syndromes, is due to postprandial hypoglycaemia caused by an excessive insulin secretion after a sharp rise in plasma glucose. Several treatments, including operation, dietary fibre and somatostatin, have been attempted to relieve dumping symptoms. These treatments take effect through modulation of plasma insulin and glucose levels, but their efficacy is still under consideration. α-Glucosidase inhibitor attenuates the postprandial increase of plasma glucose levels and is widely used for treatment of non-insulin-dependent diabetes mellitus (NIDDM). The acute effect of α-glucosidase inhibitor on late dumping syndrome has been reported by some studies with test meals. The purpose of this study was to evaluate a long-term effect of α-glucosidase inhibitor treatment with ordinary meals in late dumping patients with NIDDM because administration of α-glucosidase inhibitor is only ethically allowed for diabetic patients in Japan. Six late dumping patients with NIDDM were orally administered α-glucosidase inhibitor, acarbose (50 or 100 mg), three times a day before each meal for 1 month. Diurnal changes of plasma glucose, insulin and pancreatic glucagon levels were compared before and after the α-glucosidase inhibitor treatment. All patients had late dumping-related symptoms, such as weakness, palpitation and dizziness before the induction of α-glucosidase inhibitor treatment. Patients suffered from a rapid fall in plasma glucose levels from hyperglycaemia at the same time as dumping symptoms. These late dumping-related symptoms disappeared and a rapid change of plasma glucose and insulin levels were attenuated after the α-glucosidase inhibitor treatment. These data suggest a long-term therapeutic efficacy of α-glucosidase inhibitor for late dumping patients.     

Effects of Isoquinolinesulphonamide Compounds on Multidrug-resistant P388 Cells

Abstract— The effects of eight isoquinolinesulphonamide compounds on resistance to vinblastine in adriamycin-resistant mouse leukaemia cells (P388/ADR) which overexpress the relative molecular weight (M_r) 140 kDa P-glycoprotein in the plasma membrane were investigated. N-[2-(Methylamino)ethyl]-5-isoquinolinesulphonamide (H-8) and N-(2-aminoethyl)-5-isoquinolinesulphonamide (H-9) did not reverse vinblastine resistance. N-[2-[N-[3-(4-Chlorophenyl)-2-propenyl]amino]ethyl]-5-isoquinolinesulphonamide (H-86) and N-[2-[N-[3-(4-chlorophenyl)-1-methyl-2-propenyl]amino]ethyl]-5-isoquinolinesulphonamide (H-87) caused accumulation of intracellular vinblastine and inhibition of vinblastine efflux from the cells and reversed the resistance. Addition of an aminoethyl group to the nitrogen atom of the sulphonamide group (W-66) or a formyl group at the terminal amino group (H-85) of H-86 reduced those activities. Conversion of the chlorophenyl group of H-87 to pyridinyl (H-31) or furanyl (H-34) markedly decreased activities against the drug resistance. The activity against vinblastine accumulation closely correlated with the apparent partition coefficient of compounds. These compounds dose-dependently inhibited photoaffinity labelling of a photosensitive analogue of vinblastine, N-(p-azido-(3-[¹²⁵I])salicyl)-N′-β-aminoethylvindesine ([¹²⁵I]NASV), and there was a good correlation between inhibition of [¹²⁵I]NASV-photolabelling and hydrophobicity. Although these isoquinolinesulphonamides inhibited protein kinase A with different magnitudes, this activity did not correlate with the effect on the drug resistance. These results indicate that isoquinolinesulphonamide compounds with a hydrophobic group interact with antitumour drugs on P-glycoprotein and reverse multidrug resistance without involvement of their activity on protein kinase A.     

Three-dimensional Ultrasonography Using Ultrasonic Probes by the Transpapillary Approach for Diagnosis of Pancreatobiliary Diseases

Abstract: Three-dimensional (3D) intraductal ultrasonography (IDUS) is more useful than two-dimensional IDUS for the diagnosis of pancreatobiliary disease. We investigated the advantages and disadvantages of the transpapillary approach for 3D-IDUS using a newly developed system for pancreatobiliary application. In total 12 patients with a sufficiently wide orifice were examined, bile duct (BD) scanning being successful in 100% of attempted cases and main pancreatic duct (MPD) scanning in 85.7%. In all cases, acceptable radial and linear images were obtained and 3D diagnosis was accomplished. However, several primary problems were experienced; 1) The 3D probe is relatively inflexible, having a thick shaft and a long tip, such that insertion into the BD or MPD can be somewhat difficult; 2) Clear images of the BD or MPD wall were not always obtained because of artifacts produced by the 3D probe itself; 3) In some cases, linear images could not be reconstructed with BD or MPD scanning despite sufficiently clear radial scan images. In the future, development of new 3D probes with more flexible and thinner shafts, and shorter tips, should considerably enhance the diagnostic capacity of IDUS for the pancreatobiliary system.     

Ocular Membrane Permeability of Hydrophilic Drugs for Ocular Peptide Delivery

The purpose of this study is to investigate the ocular membrane permeability and the permeation mechanism of hydrophilic drugs such as thyrotropin-releasing hormone (TRH), p-nitrophenyl β-cellopentaoside (PNP) and luteinizing hormone-releasing hormone (LHRH). The penetration of hydrophilic drugs was measured across the isolated corneal and conjunctival membranes of albino rabbits using a two-chamber diffusion glass cell. The corneal permeabilities of hydrophilic drugs were much lower than those of beta blockers reported previously. The corneal penetration of TRH was the highest among the hydrophilic drugs studied. Scraping the corneal epithelium increased the penetration of hydrophilic drugs. Conjunctival membranes showed higher permeability to hydrophilic drugs compared with corneal membranes. The permeability of drugs was also analysed by Fick's equation. The partition parameter and diffusion parameter of TRH, PNP and LHRH in the cornea were lower than those in scraped cornea and conjunctiva. In addition to the data of fluorescein isothiocyanate-dextran reported previously, the permeability coefficient of hydrophilic drugs through the cornea, scraped cornea and conjunctiva correlated with molecular weight of the drugs. The diffusion parameters of hydrophilic drugs decreased with an increase of molecular weight for all ocular membranes. The extent of dependency of partition parameters on the molecular weights of drugs varied according to the ocular membrane. These results indicate that ocular membranes are sufficiently different in permeation character and mechanism to control the extent and pathway for ocular absorption of hydrophilic drugs.     

Churg–strauss syndrome: importance of colonoscopy and endoscopic biopsy in establishing diagnosis

A 31‐year‐old Japanese man was admitted with complaints of left lower abdominal pain and diarrhea. He had a history of bronchial asthma since he was 26 years old. On admission, his eosinophil count was 4100/mm ³ and increased as high as 12 000/mm ³ . A neurological examination disclosed mononeuritis multiplex with paresthesia in both lower and upper extremities. Because of hematochezia, colonoscopy was performed and disclosed multiple colonic ulcers and erosions from the rectum to the ascending colon. Endoscopic biopsy showed fibrinoid necrosis of small‐sized vessels with moderate infiltration of eosinophils in the mucosa and submucosa. He was suspected of being a case with Churg–Strauss syndrome (CSS; allergic granulomatous angiitis), and prednisolone of 30 mg/day was administered. After the administration of prednisolone, his eosinophil count decreased dramatically. His symptoms also improved gradually, except for numbness in the extremities. Three weeks later, colonoscopy revealed improvement of the mucosal appearance, but the colonic ulcers and erosions were still present. Endoscopic biopsy showed exravascular granuloma with moderate infiltration of eosinophils in the submucosa. Colonoscopy and endoscopic biopsy may be important in establishing the diagnosis of CSS with intestinal symptoms.     

Liver abscess that developed after a long interval of transcatheter arterial embolization followed by formation of hepatoduodenal fistula

A 55‐year‐old male patient with hepatocellular carcinoma underwent transcatheter arterial embolization (TAE). He became febrile and experienced pain at the right hypochondrial region 323 days later, which led to the discovery of a liver abscess that fistulated into the duodenal bulb. There have been no reports on the fistulation of liver abscesses into the digestive system following TAE. Rhodococcus equi was isolated as a causative agent, which distinguished the case further.     

Electrophysiological and Anatomical Substrates for Late Potential Recorded by Signal Averaging in Seven-Day-Old Myocardial Infarction in Dogs

A filtered QRS (fQRS) was recorded by signal averaging in 7-day-old myocardial infarction (MI) in dogs to detect late potential (LP). The criteria for the LP included a duration of fQRS (D) greater than or equal to 60 msec and a voltage in the last 15 msec (V15) less than or equal to 10 microV. These parameters were determined from the control data from 15 dogs without infarction (D: 45 to 60 msec and V15: 12.0 to 83.6 microV). On the seventh day of infarction, the D had increased from 53.5 +/- 4.7 to 62.2 +/- 9.6 msec (P less than 0.05) and the V15 decreased from 38.6 +/- 19.5 to 18.4 +/- 16.0 microV (P less than 0.01). Of 23 dogs, 14 met the LP criteria (group A) and 9 did not (group B). Sustained ventricular tachycardia (SVT) was induced in 12 group A dogs and in none of the group B dogs. The delayed epicardial activation (DEA) was recorded after the end of QRS at 5.1 +/- 4.7 sites in group A dogs and 1.3 +/- 1.8 sites in group B dogs (P less than 0.05). The maximum value of epicardial activation time was more prolonged in group A than in group B (70.0 +/- 28.3 vs 44.4 +/- 9.8 msec, P less than 0.01). The area of MI was more extensive in dogs with DEA than those without (24.9 +/- 5.8% vs 10.3 +/- 9.0% of the total left ventricular weight, P less than 0.01). In 72 of 90 sites with DEA, the thickness of the surviving epicardial muscle was less than or equal to 1 mm. The sensitivity and specificity of the criteria for LP in detecting DEA were 71.4% and 55.6%, and 100% and 81.8% for predicting inducibility of SVT. It was thus concluded that LP, reflected the DEA, was identified from infarct areas of slow conduction within a reentry circuit of SVT.     

Deficiency of endogenous prostanoids in gastric and duodenal ulcer diseases

The levels of prostaglandin E₂ (PGE₂), 6-keto-prostaglandin F₁α (PGF₁α) and thromboxane B₂ (TXB₂) in endoscopic biopsy specimens from the gastric and duodenal mucosa of healthy volunteers and ulcer patients were measured by radio-immunoassay. The PGE₂ and PGF₁α levels in the mucosa of the corpus of the stomach were lower and the TXB₂ level was higher in 10 patients with gastric ulcer in the corpus than in the 16 healthy subjects. The PGE₂ level in the antral mucosa of 14 patients with gastric ulcer in the antrum was lower than in the controls. In 18 patients with duodenal ulcer, PGE₂ deficiency was more widespread in the entire gastric and duodenal mucosa while the reduced PGF₁α level was limited in the gastric corpus. Lower levels of PGE₂ in patients with antral or duodenal ulcer and of PGE₂ and PGF₁α in patients with corpus ulcer in the anatomical mucosal area including the ulcer site may predispose the mucosa to ulceration.