Indirect impact of the COVID-19 pandemic on the incidence of non-COVID-19 infectious diseases: a region-wide, patient-based database study in Japan.

OBJECTIVES: The COVID-19 pandemic has forced people to change many behaviours, including physical distancing, hygiene measures and lifestyles. This study aimed to evaluate the indirect impact of the COVID-19 pandemic on the incidence of non-COVID-19 infections and medical care costs/visits using health insurance claims. STUDY DESIGN: This was an observational study using patient-based administrative claims covering approximately 800,000 insured persons and their dependents in the Mie Prefecture in Japan. METHODS: This study identified non-COVID-19 infectious disease incidences, number of outpatient visits and healthcare costs between 2017 and 2021. Each year was divided into quarters. The adjusted incidence rate ratios (IRRs) during the pandemic (January 2020 to September 2021) and during the prepandemic period (January 2017 to December 2019) were determined using Poisson regression. RESULTS: The adjusted influenza IRRs from April 2020 were close to zero. The incidence of upper respiratory tract infections and bacterial pneumonia was significantly reduced (IRRs range: 0.39-0.73 and 0.43-0.84, respectively). Gastrointestinal and urinary tract infection incidences decreased by approximately 30% and 10%, respectively. In contrast, sexually transmitted infections (STIs), including syphilis, gonococcal infection and Chlamydia trachomatis infection, did not decrease during the pandemic but increased significantly between April and June 2021 (adjusted IRR, 1.37; 95% confidence interval, 1.18-1.60). The adjusted IRRs for outpatient visits and healthcare costs were 0.86-0.93 and 0.91-0.97, respectively. CONCLUSIONS: In contrast to other infections, STIs did not decrease during the COVID-19 pandemic. The IRR of STIs during the pandemic period is an area of public health concern. Appropriate screening and medical consultations are strongly recommended.

Impact of intra-arterial chemotherapy including internal carotid artery for advanced paranasal sinus cancers involving the skull base.

BACKGROUND: The most significant problem of intra-arterial chemotherapy for advanced paranasal sinus carcinomas and residual cancers supplied by internal carotid artery (ICA) and involving the skull base is the lack of salvage therapies. OBJECTIVE: The objective of the study was to evaluate the usefulness of intra-arterial chemotherapy including ICA infusion for treating advanced paranasal sinus carcinomas, which have invaded the skull base. METHODS: Forty-six patients with advanced paranasal sinus carcinomas supplied by ICA were treated by intra-arterial chemotherapy using CDDP and sodium thiosulphate (STS) as a neutraliser of CDDP toxicity. After evaluating CT angiography, 150 mg m(-2) of CDDP was superselectively administered weekly to each feeding artery including ICA four times. RESULTS: The 10-year overall survival rate and progression-free survival rate were 70.7 and 60.2%, respectively. Compared with control group without infusing ICA, recurrences at anterior skullbase or anterior ethomoid sinus were significantly diminished. Of 32 patients in which the orbital apex had been invaded, 29 patients were treated with successful preservation of orbital contents. The CT angiography could efficiently determine all feeding arteries supplying the cancers. Consequently, chemotherapy could be administered on schedule, and side effects were minimal and acceptable. CONCLUSIONS: This new method has promising applications in the treatment of advanced paranasal sinus carcinomas involving the skull base.

The Culdotomy FourS Two U procedure for transvaginal access to the peritoneal cavity.

A reliable method of transvaginal access is needed for natural orifice transluminal endoscopic surgery. We introduce a new culdotomy procedure, using a technique for the creation of space in the cul-de-sac, transvaginal ultrasound, and a newly developed umbrella Hakko needle. An artificially developed, saline-containing space in the cul-de-sac was punctured by an umbrella Hakko needle from the vagina under the guidance of ultrasound. The vaginal walls on both sides of the needle were incised with an electric scalpel. In five cases with benign gynecological tumors, culdotomy was successfully performed. Operating time was less than 10 minutes and blood loss was less than 10 mL. There were no culdotomy-associated complications. This procedure, named Culdotomy FourS Two U, is a simple, safe, and reliable method for entry into the cul-de-sac in transvaginal gynecological surgeries and may have future applications in transluminal endoscopic surgery through the vagina.

Ultrasound-guided culdotomy for vaginal ovarian cystectomy using a renal balloon dilator catheter.

OBJECTIVES: To evaluate the feasibility and utility of performing ultrasound-guided culdotomy using a renal balloon dilator catheter for transvaginal ovarian cystectomies. METHODS: Culdotomy using transvaginal sonography and a Nephromax balloon dilator catheter was performed in 16 patients for the vaginal removal of benign ovarian cysts located in the cul-de-sac. Each ovarian cyst was punctured under transvaginal ultrasound guidance and the punctured site on the vaginal wall was enlarged with a dilator. The cyst was then enucleated through this vaginal wound. Preoperative characteristics of the patients, outcome, operating time, blood loss and complications of each culdotomy, and the histology of the cysts, were recorded and examined. RESULTS: We used this method on 14 patients with unilateral ovarian cysts and two with bilateral cysts. Culdotomy was performed successfully in 15 cases (94%). The mean +/- SD operating time for culdotomy was 22 +/- 11 min, and blood loss during the procedure was less than 10 mL in all cases. There were no complications including rectal injury or febrile morbidity. CONCLUSIONS: Culdotomy assisted by ultrasound imaging and a dilator is a safe, reliable and effective method for removal of benign ovarian cysts via a vaginal approach.

Keloid fibroblasts resist ceramide-induced apoptosis by overexpression of insulin-like growth factor I receptor.

Keloids are benign dermal tumors, characterized by overgrowth of lesions, invasiveness beyond the original boundary of the insult, and recurrence of lesions. The exact etiology is unknown, however. Our hypothesis is that keloids are acquired as a result of an abnormal or prolonged wound healing process, with persistent proliferation and extracellular matrix production of fibroblasts that should otherwise discontinue in normal wound healing. In this study, we examined the response of keloid fibroblasts to proapoptotic signaling. Cell-permeable ceramide, N-acetyl-D-sphingosine, induced apoptosis of dermal fibroblasts in a dose- and time-dependent manner, which was detected by phase contrast microscopy, fluorescent microscopy, the TUNEL method, flow cytometric analysis, and WST-1 assay. In contrast, keloid fibroblasts resisted apoptosis induced by N-acetyl-D-sphingosine (percent survival with 40 mM ceramide treatment for 12 h, normal versus keloid: 9.6% +/- 6.6% vs 66.8% +/- 5.5%). Western blotting analysis showed insulin-like growth factor I receptor overexpression in keloid fibroblasts, but not in normal fibroblasts. Exogenously added insulin-like growth factor I enhanced the resistance of keloid fibroblasts to ceramide-induced apoptosis. Wort- mannin, a phosphatidylinositol 3 kinase inhibitor, suppressed the antiapoptotic action of insulin-like growth factor I in keloid fibroblasts. Our results suggest that keloid fibroblasts overexpressing insulin-like growth factor I receptor are resistant to apoptosis, thus allowing persistent proliferation and production of excessive extracellular matrix. J Invest Dermatol 115:1065-1071 2000

Studies on the angioarchitecture of the posterior choroid in rat and role of posterior ciliary vein.

Vascular casts were made by injection of low-viscosity plastic in eight Wistar-Kyoto rats, and the posterior half of the ocular wall was observed using the semiultrathin section method. Veins which connect with the capillaries of the posterior choroid include a venous system independent of the cortex vein and running parallel to the long and short posterior ciliary arteries. The veins flow into a venous ring which is located in the region at which the arterial circle of Zinn is said to be. There was no structure in this region which could be described as an arterial circle. From the above findings, it is concluded that these venous systems are part of the posterior ciliary vein and that they play an important role as a pathway for irrigation of blood from the posterior choroid.

A new PCR-based assay amplifies the E6-E7 genes of most mucosal human papillomaviruses (HPV).

We established a new assay to detect the E6-E7 DNA of mucosal human papillomaviruses (HPV) by a PCR-based method using four pairs of degenerate LCR and E7 primers (LCR-E7 PCR). This assay amplifies the full length of E6 and the N-terminal part of E7. HPV typing was performed using restriction-fragment-length polymorphism (RFLP), and by analyzing the sequences of cloned PCR products. We compared this assay with the first generation hybrid captured assay (HCA-I) and the MY09/11-PCR method. LCR-E7 PCR was able to detect more than 34 mucosal HPV types and theoretically should detect two additional types. LCR-157 PCR and HCA-I detected HPV DNA in 70% (69/99) and 55% (54/99) of low-grade cervical intraepithelial lesions (LSIL), 89% (105/118) and 76% (90/118) of high-grade cervical intraepithelial lesions (HSIL), and 90% (56/62) and 79% (49/62) of invasive squamous cell carcinomas (SCC), respectively. LCR-E7 PCR was more sensitive than the HCA-1 test. Discordant results between the LCR-E7 and MY 11/09-PCR tests were observed in one of 185 (0.5%) normal samples, seven of 85 (8.2%) LSIL samples, seven of 82 (8.5%) HSIL samples, and four of 72 (5.6%) SCC samples. The discordant results were mostly observed in samples with a low-copy number of the HPV genome or with multiple HPV infection. The sensitivity of LCR-E7 PCR was equivalent to that of MY 11/09 ECR, and false positives were less frequent in LCR-E7 PCR. LCR-E7 PCR may be useful for determining the biological activity of detected HPV types, since this method amplifies the entire E6 gene.

A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering.

Microporous, non-woven poly( epsilon -caprolactone) (PCL) scaffolds were made by electrostatic fiber spinning. In this process, polymer fibers with diameters down to the nanometer range, or nanofibers, are formed by subjecting a fluid jet to a high electric field. Mesenchymal stem cells (MSCs) derived from the bone marrow of neonatal rats were cultured, expanded and seeded on electrospun PCL scaffolds. The cell-polymer constructs were cultured with osteogenic supplements under dynamic culture conditions for up to 4 weeks. The cell-polymer constructs maintained the size and shape of the original scaffolds. Scanning electron microscopy (SEM), histological and immunohistochemical examinations were performed. Penetration of cells and abundant extracellular matrix were observed in the cell-polymer constructs after 1 week. SEM showed that the surfaces of the cell-polymer constructs were covered with cell multilayers at 4 weeks. In addition, mineralization and type I collagen were observed at 4 weeks. This suggests that electrospun PCL is a potential candidate scaffold for bone tissue engineering.

Purification and characterization of a major kyotorphin-hydrolyzing peptidase of rat brain.

We purified a major kyotorphin (L-Tyr-L-Arg)-hydrolyzing peptidase (KTPase) from the rat brain, to electrophoretic homogeneity using conventional chromatographic techniques. KTPase was purified 1,660-fold with a specific activity of 161 mumol/min/mg protein and 6.8% recovery. The purified enzyme was composed of a single polypeptide with a molecular mass of 67 kDa and an isoelectric point (pI) of 5.5. KTPase has the ability to hydrolyze a variety of natural dipeptides. It also liberated NH2-terminal tyrosine from Tyr-Gly-Gly and Tyr-Tyr-Leu. Bestatin and arphamenine B were potent inhibitors of this enzyme, while amastatin and puromycin had little effect. An excess of anti-KTPase antibody raised in a white rabbit precipitated approximately 80% of the kyotorphin-hydrolyzing activity in the cytosol of rat brain. These data suggested that 67 kDa KTPase has a role in the degradation of kyotorphin within neuronal cells of the rat brain.

Endoscopic sphincterotomy for the treatment of biliary sump syndrome.

Biliary "sump" syndrome is a rare but embarrassing problem after side-to-side choledochojejunostomy or choledochoduodenostomy. Four patients with they syndrome treated nonoperatively by endoscopic sphincterotomy are described. Three of these had had choledochojejunostomy previously and the other inadvertent choledochoduodenostomy at prior common duct exploration. Cholangitic symptoms or biliary obstruction disappeared and the patients have been well for periods ranging from 2 to 5.5 years. Endoscopic sphincterotomy can eliminate the stasis area of the common duct distal to the lateral anastomosis, obviating relaparotomy, and may deserve first consideration in patients with the sump syndrome.

Two approaches for electrohydraulic lithotripsy in the common bile duct.

Electrohydraulic lithotripsy is a method used to break up a stone by electric discharge in the presence of liquid medium. After the effect of crushing gallstones was tested in vitro, efficacy and safety of this method were investigated with 11 mongrel dogs. When the electrode was in touch with or close to the bile duct wall, the discharge caused perforation or potentially serious mucosal injury. However, a stone held in a basket catheter combined with the lithotripsy probe was fragmented safely in the bile duct in all the animals. Bile duct manometry showed a transient fall, which was followed by a slight increase, of the pressure on crushing the stone. After these studies in animals, three patients with stones in the common bile duct were treated successfully with the device via the percutaneous transhepatic route (one patient) or through the duodenoscopic route (two patients). Two approaches are now available for electrohydraulic lithotripsy in the common bile duct.

Electrohydraulic lithotripsy of intrahepatic stones during choledochoscopy.

In two patients, electrohydraulic lithotripsy was used under direct vision during choledochoscopy to fragment intrahepatic calculi above bile duct strictures, which were difficult to remove by ordinary choledochoscopic methods. Choledochoscopy was performed after dilation of a percutaneous transhepatic tract in one patient and after intubation of the subcutaneous blind jejunal limb of a previous Roux-en-Y intrahepatic cholangiojejunostomy in the other. Both patients were treated without any complications. Electrohydraulic lithotripsy during choledochoscopy is a safe and effective method to fragment stones and facilitate their removal.

Construction of a plasmid vector for transformation of Porphyromonas gingivalis.

A host-vector system for transformation of Porphyromonas gingivalis was constructed using a set (1) strains that can incorporate plasmid DNA by electroporation regardless of its source and (2) stable vector plasmids with a selectable marker. First, restriction-negative mutants were isolated, because P. gingivalis possesses restriction modification systems by which DNA introduced by transformation even from heterologous strains of the same species is excluded. For screening of the mutants, plasmid pE5-2 was employed since it could be transconjugated (mobilized) to P. gingivalis from Escherichia coli and is able to replicate in this species, albeit not stably. pE5-2 DNA prepared from E coli was introduced by electroporation into chemically mutagenized P. gingivalis cells. By this method, three putative restriction-negative clones were selected. These strains exhibited a capacity for electroporation with plasmid DNAs both from E. coli and from various P. gingivalis strains at a similar efficiency. Using one of the derivatives thus obtained, YH522, we then screened for plasmids that could replicate stably in P. gingivalis. Since no plasmids were found from P. gingivalis, cryptic plasmids from other species of black-pigmented oral anaerobic rods were examined for their ability to transform P. gingivalis. A series of plasmids constructed by ligation with pBR322 for replication in E. coli and the EcoRI-B fragment from pBF4 containing erythromycin resistance were prepared from E. coli and were used for electroporation of P. gingivalis. Among these, a recombinant plasmid containing the replicon of pYHBA1 from Porphyromonas asaccharolytica, designated pYH400, was found to be incorporated into the restriction-negative P. gingivalis strain and replicated stably. This set of recipient strains and stable plasmids with a selectable marker constitutes the first practical host-vector system for this species.

Reduced fimbria-associated activities of Porphyromonas gingivalis induced by recombinant fimbrial expression.

The adhesion properties of the recombinant fimbriae (r-fimbriae) recovered from a YH522 transformant of Porphyromonas gingivalis which harbors a chimeric plasmid, pYHF2, containing the fimA gene of strain 381 were compared with those of the endogenous fimA fimbriae of strain 33277. The adhesion level of the r-fimbriae to Actinomyces viscosus was clearly lower than that of the endogenous fimbriae. In addition, the r-fimbriae were shown to lack some minor components detectable in the endogenous fimbriae. The plasmid pYHF2 prepared from the YH522 transformant was then transformed into six different P. gingivalis strains and the resultant pYHF2-containing strains were examined for their fimbrial expression. In spite of the presence of a considerable diversity in the expression level of the r-fimbriae among these transformants, it was evident that the strains expressing higher levels of the r-fimbriae exhibited a greater decrease in adhesion activity to other bacteria and to oral epithelial cells, as well as in self-aggregation.

Platelet aggregating activity of plasma in patients with thrombotic thrombocytopenic purpura evaluated by a particle counting method using light scattering.

The platelet aggregating activity of plasma obtained from five patients with thrombotic thrombocytopenic purpura (TTP) was evaluated by a particle counting method using light scattering. When normal platelets were suspended in the plasma obtained from TTP patients, small aggregate formation was observed after stirring at 1000 rpm without the addition of platelet aggregating agents; no aggregate was observed, however, in the plasma obtained from healthy donors. Since the inhibitory effect of the addition of normal plasma to TTP plasma on this reaction was dose-dependent and not additive, the efficacy of plasma therapy was not confirmed. Small aggregates were formed in the high molecular weight fraction (HMWF) of TTP plasma but not in the low molecular weight fraction (LMWF), suggesting that the platelet aggregating activity existed in HMWF. Among the antiplatelet agents usually used for TTP, dipyridamole was more effective for the inhibition of this reaction than aspirin. This spontaneous platelet aggregation reaction by a particle counting method using light scattering could be useful for evaluating the platelet aggregating activity in patients with TTP.

Enhancing effect of platelets on staphylokinase-mediated clot lysis and plasminogen activation.

The effects of platelets on clot lysis and plasminogen activation by staphylokinase (SAK) were investigated. At concentrations ranging from 2 x 10(-7) to 1 x 10(-5)g/ml of SAK, the lysis time of platelet-rich plasma clots (PRP-clots) was shorter than that of platelet-poor plasma clots (PPP-clots). This reduction of clot lysis time was observed in a dose-dependent manner on platelet count in PRP. The activation rate of plasminogen by SAK measured by the amidolytic method using S-2251 was enhanced by the addition of washed platelets. These enhancing effects of platelets on clot lysis and plasminogen activation were not altered by pretreatment of platelets with indomethacin and theophylline, but were diminished by platelet disruption. Thus, we concluded that platelets enhance fibrinolytic activity of SAK, and this effect is not due to the release reaction or intracellular contents of platelets, but to the existence of platelet surface in the intact shape as a catalytic site for fibrinolysis.

Effects of transjugular intrahepatic portosystemic shunt (TIPS) on esophageal motor function and gastroesophageal reflux.

The effects of transjugular intrahepatic portosystemic shunt (TIPS) placement on esophageal motor function and gastroesophageal reflux were investigated in patients with esophageal varices. In six men with esophageal varices, esophageal manometry and upper gastrointestinal endoscopy were performed before and 15-20 days after TIPS placement. Intraesophageal pH monitoring was performed in the four patients with severe esophageal varices (defined as the largest sized varices) following TIPS placement. Findings were compared with those in six healthy men (controls) who underwent esophageal manometry and intraesophageal pH monitoring. The esophageal varices resolved or were reduced after TIPS placement. Resting lower esophageal sphincter (LES) pressures were similar in the study group before and after TIPS placement and in the control subjects. The incidence and progression of esophageal contractions were similar in the study group before and after TIPS placement and in the control subjects. At 3 cm above the LES, the amplitude of esophageal contraction after TIPS placement was significantly higher than that before TIPS placement. At 3 and 8 cm above the LES, the amplitude of esophageal contraction in the control subjects was significantly higher than that in the study group before and after TIPS placement. Esophageal acid exposure time after TIPS placement was similar to that in the controls. TIPS placement is a useful treatment that improves esophageal motor function without the occurrence of pathologic gastroesophageal reflux.

Human papillomaviruses in the normal oral cavity of children in Japan.

The purpose of this study was to determine the frequency of human papillomavirus (HPV) infections in the normal oral cavity of children in Japan. Oral squamous cell specimens were collected from 77 children (44 boys and 33 girls), aged 3 and 5 years. Extracted DNA was evaluated for HPV infections by polymerase chain reaction (PCR) methods, using consensus primers for the L1 region, specific primers, and direct DNA sequencing analysis. Thirty-seven of 77 specimens (48.1%) were positive for HPV DNA. Positive rates of boys and girls in all specimens were 28.3 (22/77) and 19.5 (15/77)%, respectively. The positive rate in 3-year-old children was 45.2 (14/31)%, and positive rates in boys and girls were 52.6 (10/19) and 33.3 (4/12)%, respectively. The positive rate in 5-year-old children was 50.0 (23/46)%, and positive rates in boys and girls were 48.0 (12/25) and 52.4 (11/21)%, respectively. HPV types were determined by specific PCR and direct DNA sequencing analysis. Frequent HPV types in the specimens of all children were HPV-16 (11/37; 29.7%),-1 (6/37; 16.2%),-2 (6/37; 16.2%),-75 (6/37; 16.2%). The results of the present investigation indicate that many HPVs, including HPV-16 (a high-risk type for cancer), are present in the oral cavity of 3- and 5-year-old children. It is suggested, therefore, that the oral cavity is already a reservoir of HPVs in childhood where later HPV-associated diseases, such as oral cancer and other oral lesions, may develop.

The long-term fate of the gallbladder after endoscopic sphincterotomy. Complete follow-up study of 122 patients.

One hundred twenty-two patients with common bile duct stones and intact gallbladders underwent endoscopic sphincterotomy without cholecystectomy and were followed for 6 months to 9 years (mean 3 years). Nineteen patients died from unrelated causes. One hundred of 103 surviving patients (97 percent) were asymptomatic, whereas 3 had complaints. Acute cholecystitis did not occur in 91 patients without gallstones, whereas it did occur in 5 of 31 patients (16 percent) with gallstones (25 patients) or nonvisualization of the gallbladder (6 patients). Two patients in the former subgroup had formation of new gallstones. We conclude that cholecystectomy should be advocated whenever possible in patients with gallstones or nonvisualization of the gallbladder after endoscopic sphincterotomy due to the high incidence of acute cholecystitis in this subgroup and that operation is not necessary in patients without gallstones; however, one should be aware of possible formation of new stones in the gallbladder.

Nonoperative removal of giant common bile duct calculi.

Endoscopic sphincterotomy has allowed us to extract relatively large stones from the common bile duct as compared with other methods utilizing a T-tube tract or the percutaneous transhepatic route. Twenty-four patients with large stones over 20 mm in diameter were selected and reviewed from a series of 469 sphincterotomy patients. Eleven stones passed into the duodenum spontaneously, the maximal size of which was 30 by 43 mm. Passage occurred within 4 days after sphincterotomy in 27 percent, 5 to 7 days after the procedure in 55 percent, and 8 to 13 days after the procedure in 18 percent and was accompanied by cholangitis in 55 percent of the patients. The small diameter of the stone and common bile duct dilatation down to the distal end seemed to be the factors favoring stone delivery. Five stones were removed using ordinary basket catheters by duodenoscopy; however, the largest one required 28 attempts. More recently, four stones were efficiently extracted after destruction by electrohydraulic or mechanical lithotripsy. Failure of removal in five patients was mainly due to a lack of space around the stone for basket manipulation or occurrence of severe cholangitis. Further refinements in technique in this regard are needed.