Relationship between perioperative cardiopulmonary bypass time, platelet count, fibrinogen level, rotational thromboelastometry data, antithrombin level, and blood loss volume and the effects of deep hypothermic circulatory arrest: An observational study.

INTRODUCTION: We hypothesized that perioperative fibrinogen level, platelet count, and rotational thromboelastometry (ROTEM) data values decrease in proportion to cardiopulmonary bypass (CPB) time, particularly in patients who underwent deep hypothermic circulatory arrest (DHCA). METHODS: A total of 160 patients were enrolled and divided into the following three groups depending on CPB time: <2-h, 2- 3-h, and >3-h groups. Blood samples were obtained during CPB weaning. Platelet count, ROTEM data, fibrinogen level, and antithrombin level were determined. For propensity matching, we selected 15 patients who underwent DHCA and 15 patients who did not undergo DHCA and used propensity scores to match CPB time and other characteristics. RESULTS: The <2-h, 2-3-h, and >3-h groups included 74, 63, and 23 patients, respectively. No significant differences in platelet count and fibrinogen level were observed between the groups. Antithrombin level and amplitude of clot firmness at 10 min in the EXTEM and FIBTEM tests were lowest in the >3-h group. Similarly, blood loss volume and transfusion volume were highest in the >3-h group. Significant differences in platelet count, ROTEM data, lowest esophageal and bladder temperatures, and transfusion volume were observed between patients who underwent DHCA and patients who did not undergo DHCA. CONCLUSIONS: The longer the CPB time, the greater the perioperative blood loss volume and transfusion volume, particularly if CPB time is greater than 3 hours. Sub-group analysis revealed that DHCA affects perioperative platelet count and function as well as blood loss volume.

MEASUREMENT OF INTERNAL RADIATION DOSE DISTRIBUTION IN CT EXAMINATIONS USING POLYETHYLENE TEREPHTHALATE RESIN.

This study proposes a new dosimetry method for the estimation of the internal radiation dose distribution of a subject undergoing computed tomography (CT) examinations. In this novel method, dose distribution of a subject by CT scans was estimated based on radiophotoluminance distribution with polyethylene terephthalate (PET) resin which was cut to the average head size of a Japanese 1-year-old child. The difference in dose distribution depending on the type of bowtie filter was visualized by imaging luminance distribution with the PET phantom using a charge-coupled device camera. Dose distribution images simulated from a water phantom of the same size as the PET phantom were compared with the luminance distribution images. The linear correlation was demonstrated between luminance of the PET phantom and the simulated water dose. In comparison with the simulated water doses and the converted water doses from luminance of the PET phantom, the relative differences were within 20%.

Scattered radiation from dental metallic crowns in head and neck radiotherapy.

We aimed to estimate the scattered radiation from dental metallic crowns during head and neck radiotherapy by irradiating a jaw phantom with external photon beams. The phantom was composed of a dental metallic plate and hydroxyapatite embedded in polymethyl methacrylate. We used radiochromic film measurement and Monte Carlo simulation to calculate the radiation dose and dose distribution inside the phantom. To estimate dose variations in scattered radiation under different clinical situations, we altered the incident energy, field size, plate thickness, plate depth and plate material. The simulation results indicated that the dose at the incident side of the metallic dental plate was approximately 140% of that without the plate. The differences between dose distributions calculated with the radiation treatment-planning system (TPS) algorithms and the data simulation, except around the dental metallic plate, were 3% for a 4 MV photon beam. Therefore, we should carefully consider the dose distribution around dental metallic crowns determined by a TPS.

The role of inhibitor of DNA-binding (Id1) in hyperproliferation of keratinocytes: the pathological basis for middle ear cholesteatoma from chronic otitis media.

OBJECTIVES: A hallmark of cholesteatoma is hyperproliferation of keratinocytes with abundant production of keratins in the middle ear under chronic inflammatory conditions. However, little is known about the driving force of cellular proliferation and keratin production of cholesteatomal matrix. The purpose of this study was to investigate the cellular proliferation and keratin production of keratinocytes under the influence of Id1, a candidate transcription factor to cell proliferation. MATERIALS AND METHODS: Keratinocytes were transfected with Id1 and the responses of keratinocytes to Id1 were studied by using cellular and molecular biologic methods. RESULTS: Id1 positively contributed to the cell cycle progression and negatively to the p16(Ink4a) downregulation via the nuclear factor-kappa B (NF-κB)/cyclin D1 pathway. Id1 significantly increased the promoter activity of NF-κB which, in turn, up-regulated the expression of cyclin D1 and keratin 10 in keratinocytes. Specific NF-κB inhibitors (pyrrolidine dithiocarbamate, PDTC), or dominant-negative inhibitor (I kappa B alpha mutant, IκBαM) abrogated the Id1-induced cell proliferation and keratin 10 production whereas p65, a subunit of the NF-κB heterodimer and an enhancer of the NF-κB activity, strengthened the Id1-induced cell proliferation and keratin 10 production. CONCLUSIONS: Id1 contributed to hyperproliferation of keratinocytes via enhancement of cell cycle progression, removal of cell cycle inhibition, and simultaneously increased keratin production.

Dosimetric evaluation of nuclear interaction models in the Geant4 Monte Carlo simulation toolkit for carbon-ion radiotherapy.

We tested the ability of two separate nuclear reaction models, the binary cascade and JQMD (Jaeri version of Quantum Molecular Dynamics), to predict the dose distribution in carbon-ion radiotherapy. This was done by use of a realistic simulation of the experimental irradiation of a water target. Comparison with measurement shows that the binary cascade model does a good job reproducing the spread-out Bragg peak in depth-dose distributions in water irradiated with a 290 MeV/u (per nucleon) beam. However, it significantly overestimates the peak dose for a 400 MeV/u beam. JQMD underestimates the overall dose because of a tendency to break a nucleus into lower-Z fragments than does the binary cascade model. As far as shape of the dose distribution is concerned, JQMD shows fairly good agreement with measurement for both beam energies of 290 and 400 MeV/u, which favors JQMD over the binary cascade model for the calculation of the relative dose distribution in treatment planning.

A woman who required long-term mechanical ventilation to treat limbic encephalitis during pregnancy.

We describe our experience with a woman who had severe non-herpetic acute limbic encephalitis at 20 weeks' gestation. Despite receiving mechanical ventilation for about 3 months because of impaired consciousness and frequent convulsions, she had a normal delivery and an uneventful recovery with no sequelae. The patient did not respond to treatment with antiviral agents. Anticonvulsant agents were given while monitoring plasma drug concentrations. Early treatment and the prevention of complications apparently contributed to good outcomes in the mother and child.

The LET spectra at different penetration depths along secondary 9C and 11C beams.

Owing to the potentially therapeutic enhancement of delayed particles in treating malignant diseases by radioactive 9C-ion beam, LET spectra at different penetration depths for a 9C beam with 5% momentum spread, produced in the secondary beam line (SBL) at HIMAC, were measured with a multi-wire parallel-plate proportional counter. To compare these LET spectra with those of a therapeutic 12C beam under similar conditions, the 12C beam was replaced with an 11C beam, yielded in the SBL as well and having almost the same range as that of the 9C beam. The LET spectra of the 9C beam and its counterpart, i.e. the 11C beam, at various depths were compared, especially around the Bragg peak regions. The results show that nearby the Bragg peak lower LET components decreased in the LET spectra of the 9C beam while extra components between the LET peak caused by the primary beam and the lower components due to the fragments could be observed. These additional contributions in the LET spectra could be attributed to parts of the emitted particles from the radioactive 9C ions with suitable conditions regarding the LET counter. Integrating these LET spectra in different manners, depth-dose and dose-averaged LET distributions were obtained for the 9C and 11C beams, forming the basic data sets for further studies. In general, the depth-dose distributions of the 9C and 11C beams are comparative, i.e. almost the same peak-to-plateau ratio. The ratio for the 9C beam, however, has room to increase due to the geometric structure limitation of the present detector. The dose-averaged LETs along the beam penetration are always lower for the 9C beam than for the 11C beam except at the falloff region beyond the Bragg peak. Applying the present depth-dose and dose-averaged LET data sets as well as the essential radiobiological parameters obtained with 12C beams previously for HSG cells, an estimate concerning the HSG cell surviving effects along the penetration of the 9C and 11C beams shows that lower survival fractions for the 9C beam at the distal part of the Bragg peak, corresponding to the stopping region of the incoming 9C ions, can be expected when the same entrance dose is given. It is still hard to appreciate the potential of 9C beams in cancer therapy based on the present LET spectrum measurement, but it provides a substantial basis for upcoming radiobiological experiments.

Haptic reproduction and interactive visualization of a beating heart for cardiovascular surgery simulation.

This paper aims to achieve haptic reproduction and real-time visualization of a beating heart for cardiac surgery simulation. Unlike most forgoing approaches, the authors focus on time series datasets and propose a new framework for interactive simulation of active tissues. The framework handles both detection and response of collisions between a manipulator and a beating virtual heart. Physics-based force feedback of autonomous cardiac motion is also produced based on a stress-pressure model, which is adapted to elastic objects filled with fluid. Time series datasets of an adult man were applied to an integrated simulation system with a force feedback device. The system displays multi-dimensional representation of a beating heart and provides a basic training environment for surgical palpation. Finally, results of measurement and medical assessment confirm the achieved quality and performance of the presented framework.

PAF mediates cigarette smoke-induced goblet cell metaplasia in guinea pig airways.

Goblet cell metaplasia is an important morphological feature in the airways of patients with chronic airway diseases; however, the precise mechanisms that cause this feature are unknown. We investigated the role of endogenous platelet-activating factor (PAF) in airway goblet cell metaplasia induced by cigarette smoke in vivo. Guinea pigs were exposed repeatedly to cigarette smoke for 14 consecutive days. The number of goblet cells in each trachea was determined with Alcian blue-periodic acid-Schiff staining. Differential cell counts and PAF levels in bronchoalveolar lavage fluid were also evaluated. Cigarette smoke exposure significantly increased the number of goblet cells. Eosinophils, neutrophils, and PAF levels in bronchoalveolar lavage fluid were also significantly increased after cigarette smoke. Treatment with a specific PAF receptor antagonist, E-6123, significantly attenuated the increases in the number of airway goblet cells, eosinophils, and neutrophils observed after cigarette smoke exposure. These results suggest that endogenous PAF may play a key role in goblet cell metaplasia induced by cigarette smoke and that potential roles exist for inhibitors of PAF receptor in the treatment of hypersecretory airway diseases.

Interspecies transmission of feline immunodeficiency virus from the domestic cat to the Tsushima cat (Felis bengalensis euptilura) in the wild.

Feline immunodeficiency virus (FIV) was isolated from a wild-caught Tsushima cat (Felis bengalensis euptilura), an endangered Japanese nondomestic subspecies of leopard cat (F. bengalensis). Phylogenetic analysis of the env gene sequences indicated that the FIV from the Tsushima cat belonged to a cluster of subtype D FIVs from domestic cats. FIVs from both the Tsushima cat and the domestic cat showed similar levels of replication and cytopathicity in lymphoid cell lines derived from these two species. The results indicated the occurrence of interspecies transmission of FIV from the domestic cat to the Tsushima cat in the wild.

Mutagenic activation of 3-methoxy-4-aminoazobenzene by mouse renal cytochrome P450 CYP4B1: cloning and characterization of mouse CYP4B1.

A new P450 responsible for mutagenic activation of 3-methoxy-4-aminoazobenzene (3-MeO-AAB) which is a potent procarcinogen was purified from renal microsomes of male mice using an index of umu gene expression. The purified P450 had high bioactivation toward 3-MeO-AAB and also 2-aminofluorene and 2-aminoanthracene. The antibody against this P450 completely inhibited mutagenic activation of 3-MeO-AAB of mouse renal microsomes. With immunoblotting, this form was present abundantly in renal microsomes of male mice but not in those of female mice. This P450 was also present in pulmonary microsomes of male and female mice but not in hepatic microsomes. The NH2-terminal amino acid sequence analysis indicated that this form belonged to the CYP4B subfamily. Thus, mouse kidney cDNA library was screened with rat CYP4B1 probe. The cDNA-deduced amino acid sequence of isolated cDNA consisted of 511 amino acids and bore 90, 86, and 84% similarities to rat, rabbit, and human CYP4B1, respectively. The NH2-terminal amino acid sequence of the purified renal P450 and amino acid sequence of BrCN-digested peptides from the purified P450 agreed with the cDNA-deduced amino acid sequence. These results suggest that CYP4B1 is a major form in renal microsomes of male mice and plays a major role in mutagenic activation of 3-MeO-AAB. In extrahepatic tissue, CYP4B1 may contribute to chemical carcinogenesis.

Effect of iron as a new type of phosphate binder in hemodialysis patients.

Hyperphosphatemia is one of the major problems requiring management in the majority of hemodialysis patients and they require phosphate-binding agents to control the hyperphosphatemia. Aluminum hydroxide and calcium compounds are used currently as phosphate-binding agents to treat hyperphosphatemia, but these compounds can cause undesirable side effects. Therefore, the development of new phosphate-binding agents is imperative. It is well known that oral and intravenous administration of iron causes hypophosphatemia. We hypothesized that this side effect of iron may be beneficial for the treatment of hyperphosphatemia in hemodialysis patients. Consequently, we conducted a fundamental and clinical investigation of the effects of iron administration. Membrane permeability of phosphorus in a mixture of sodium ferrous citrate and dessicated aluminium hydroxide in the presence of hydrogenated lecithin as a phosporic compound was examined. Fifteen patients undergoing hemodialysis were treated with 150 mg of sodium ferrous citrate given orally for eight weeks. The permeability of the filtering membrane to phosphorus decreased in accordance with the dosage of sodium ferrous citrate and dessicated aluminum hydroxide. The degree of phosphate-binding effect of sodium ferrous citrate was larger than that of dessicated aluminum hydroxide. Serum phosphorus decreased significantly during the experiment. These results suggest that the oral administration of sodium ferrous citrate as a new phosphate binder is a useful therapeutic method for hemodialysis in patients with hyperphosphatemia.

A case of acquired petrous cholesteatoma associated with insidious middle ear infection treated by staging the surgical procedures.

Surgical treatment of petrous cholesteatoma is difficult, especially in infected cases, since it often involves vital structures. We report the case of a patient successfully treated for an infected petrous cholesteatoma by staging the surgical procedures to reduce the risk of intracranial complications. The patient, a 53-year-old man, was referred to our hospital because of vertigo during coughing or strenuous effort. The left side mastoid cavity was open to the external ear canal and wholly covered with cholesteatoma epithelium with purulent discharge. The superior basal turn of the cochlea, superior and posterior semicircular canals, and roof of the internal auditory canal were eroded. Conservative treatment was not effective in eradicating the otorrhea. Four weeks after the first operation (radical mastoidectomy), the second operation was conducted following a combined middle cranial fossa and transmastoid approach. The postoperative course was uneventful. Normal facial nerve function was preserved and unsteadiness disappeared, but hearing could not be preserved. The MRI examination, performed one year after surgery, did not reveal any evidence of residual cholesteatoma.

[Monocular indirect argon laser photocoagulation for advanced retinopathy of prematurity].

A retrospective study of monocular indirect argon laser retinal photocoagulation for retinopathy of prematurity (ROP) was performed on 53 eyes of 36 premature infants, admitted to the neonatal intensive care unit (NICU) of Juntendo hospital from Jan. 1988 to Dec. 1990. The argon laser beam was delivered from an argon laser source located in the outpatient clinic to the NICU through a 50-meter fiber-optic cable. Thirty-eight eyes of 27 infants showing stage 3 middle substage of ROP retained a mild grade of cicatrical ROP. Fifteen eyes of 8 infants showed "Plus disease". Five eyes of these retained a severe grade of cicatrical ROP. The success rate of ROP treatment by laser photocoagulation was more satisfactory than in xenon are photocoagulation with cryotherapy. This method has slight technical difficulties, but the infants could be treated in a supine position in the incubators. Thus, monocular indirect argon laser retinal photocoagulation is a useful method in the treatment of ROP.

Transgenic Drosophila carrying mammalian cytochrome P-4501A1: an application to toxicology testing.

Transgenic Drosophila which carry a canine cytochrome P-450 were established and evaluated for its value on toxicology testing. Dah1, a cDNA clone for the canine hepatic P-4501A1, was ligated between the promoter of Drosophila heat-shock protein gene and the terminator of actin 5C gene, and then microinjected into Drosophila embryos with a transposon P element. The injected DNA was stably integrated into chromosomal DNA in germ line cells. After heat-shock treatments, transgenic larvae produced mRNA and a detectable amount of protein that cross-reacted with antibodies against rat P-4501A1. The ability of transgenic flies to activate procarcinogens was monitored in the DNA repair test with the endpoint being preadult mortality of repair-defective mei-9a mei-41D5/Y males. Heat-shock treatments of larvae showed that the repair-defective males carrying the P-4501A1 transgene were killed by lower concentrations of 7,12-dimethylbenz[a]anthracene than their non-transgenic or non heat-shocked counterparts. Coadministration of alpha-naphthoflavone, one of the inhibitors of P-4501A subfamily, cancelled the enhanced mortality of transgenic males, supporting that 7,12-dimethylbenz[a]anthracene was metabolized to its genotoxic form by the expressed P-4501A1 enzyme. This study indicates a potential utility of transgenic Drosophila for screening mammalian promutagens and procarcinogens.

Molecular cloning of monkey liver cytochrome P-450 cDNAs: similarity of the primary sequences to human cytochromes P-450.

Three cDNAs coding for monkey cytochrome P-450 (P450) 2C, 2E and 3A (MKmp13, MKj1 and MKnf2, respectively) were isolated from a lambda gt11 cDNA library of a liver from a 3-methylcholanthrene (3MC)-treated crab-eating monkey, using cDNA fragments for human P450 2C, 2E and 3A as respective probes. MKmp13 and MKnf2 were 1901 and 2032 bp long, containing entire coding regions for polypeptides of 490 and 503 residues, respectively. The deduced N-terminal amino acid sequences of MKmp13 and MKnf2 were identical with those of P450-MK1 and P450-MK2, which had been purified from liver microsomes of untreated and polychlorinated biphenyl (PCB)-treated crab-eating monkeys, respectively. MKj1 was 1508 bp long, encoding a polypeptide of 449 residues, which is presumed to lack N-terminal 45 residues as compared with the sequence for human P450 2E1. Northern blot analysis indicated that monkey P450 2C, 2E and 3A mRNAs were expressed constitutively in monkey livers. P450 2E and 3A mRNAs were induced by both 3MC and PCB, while P450 2C mRNA was induced only by PCB. The deduced amino acid sequences of four monkey cytochrome P-450 cDNAs, including P450 1A1 (MKah1) which we isolated previously, were more than 92% identical with those of corresponding human cytochrome P-450 cDNAs.