17ß-Estradiol induces proliferation of endometrial NK cells (CD56+) in postmenopausal women.

OBJECTIVE: The aim of this report was to evaluate the impact of hormone replacement therapy (HRT) on lymphocytic infiltration of the endometrium in postmenopausal women. METHOD: This study included 58 Japanese patients who had undergone hysterectomy at the University Hospital of Occupational and Environmental Health, Japan. Before surgery, nine patients had received 17ß-estradiol (E2), 0.72 mg transdermally for 2-8 weeks (E2 group); 16 patients had received an Estra-1,3,5(10)-triene-3,16α, 17ß-triol (E3) vaginal tablet 0.5 mg per month five times (E3 group); and 19 patients had received 17ß-estradiol, 0.62 mg, and norethindrone acetate (P), 2.70 mg for 3-16 weeks (E2 + P group). Fourteen patients received no HRT (control group). We examined uterine tissue specimens immunohistochemically for CD45+, CD3+, CD4+, CD8+, CD20+, CD56+, and Ki67 antigen-positive cells. RESULTS: The numbers of CD56 + cells were significantly increased in the E2 group compared with all other groups (E2 vs. E3: 7.0 vs. 0.75, p = 0.017; E2 vs. E2 + P: 7.0 vs. 0.58, p = 0.009; E2 vs. CONTROL: 7.0 vs. 0.43, p = 0.010). The numbers of CD3+ cells were significantly increased in the E2 group compared with the control group (149.3 vs. 42.6, p = 0.008). CONCLUSION: 17ß-Estradiol induced the proliferation of endometrial uterine natural killer cells (CD56+) in postmenopausal women.

Fast Heating of Imploded Core with Counterbeam Configuration.

A tailored-pulse-imploded core with a diameter of 70 µm is flashed by counterirradiating 110 fs, 7 TW laser pulses. Photon emission (>40 eV) from the core exceeds the emission from the imploded core by 6 times, even though the heating pulse energies are only one seventh of the implosion energy. The coupling efficiency from the heating laser to the core using counterirradiation is 14% from the enhancement of photon emission. Neutrons are also produced by counterpropagating fast deuterons accelerated by the photon pressure of the heating pulses. A collisional two-dimensional particle-in-cell simulation reveals that the collisionless two counterpropagating fast-electron currents induce mega-Gauss magnetic filaments in the center of the core due to the Weibel instability. The counterpropagating fast-electron currents are absolutely unstable and independent of the core density and resistivity. Fast electrons with energy below a few MeV are trapped by these filaments in the core region, inducing an additional coupling. This might lead to the observed bright photon emissions.

Impact of a ß-blocker and/or acute hemodilution on cerebral oxygenation during apneic hypoxia.

BACKGROUND: ß-blockers reduce the tolerance for acute hemodilution by decreasing cerebral oxygenation and may contribute to the incidence of stroke. We hypothesized that ß-blockers also increase the risk for cerebral hypoxia when apneic hypoxia occurs. METHODS: After induction of isoflurane, 14 swine (mean ± SD =25.3 ± 0.8 kg) were studied using 200 µg/kg/min of landiolol or saline (control group) in three sequential stages: before, during, and after landiolol (saline) infusion. In each stage, after 5 min of mechanical ventilation with 100% oxygen, apnea was induced until the time to < 70% oxygen saturation. Hemodynamic and blood gas variables were measured, and the cerebral tissue oxygenation index (TOI) was recorded by near infrared spectroscopy (apnea experiment). After these steps, hemodilution was induced by hemorrhage of 600 ml and infusion of the same volume of hydroxyethylstarch, and the apnea experiments were then conducted before, during, and after landiolol (saline) infusion similarly to before hemodilution. RESULTS: Landiolol decreased TOI at 1 min after apnea and at SpO2 < 70% by 3.3% and 7.0% from each corresponding value at baseline, and by 13.1% and 20.3% during hemodilution. Landiolol shifted the relationship between TOI and arterial hemoglobin oxygen saturation (SaO2 ) or arterial partial pressure of oxygen (PaO2 ) to the left; and reduced TOI at similar arterial blood oxygenation. This phenomenon was marked during hemodilution. CONCLUSIONS: Landiolol reduces cerebral tissue oxygenation during apneic hypoxia. ß-blockers increase the risk for cerebral hypoxia when apneic hypoxia occurs, especially during acute hemodilution.

Direct heating of a laser-imploded core by ultraintense laser-driven ions.

A novel direct core heating fusion process is introduced, in which a preimploded core is predominantly heated by energetic ions driven by LFEX, an extremely energetic ultrashort pulse laser. Consequently, we have observed the D(d,n)^{3}He-reacted neutrons (DD beam-fusion neutrons) with the yield of 5×10^{8} n/4π sr. Examination of the beam-fusion neutrons verified that the ions directly collide with the core plasma. While the hot electrons heat the whole core volume, the energetic ions deposit their energies locally in the core, forming hot spots for fuel ignition. As evidenced in the spectrum, the process simultaneously excited thermal neutrons with the yield of 6×10^{7} n/4π sr, raising the local core temperature from 0.8 to 1.8 keV. A one-dimensional hydrocode STAR 1D explains the shell implosion dynamics including the beam fusion and thermal fusion initiated by fast deuterons and carbon ions. A two-dimensional collisional particle-in-cell code predicts the core heating due to resistive processes driven by hot electrons, and also the generation of fast ions, which could be an additional heating source when they reach the core. Since the core density is limited to 2 g/cm^{3} in the current experiment, neither hot electrons nor fast ions can efficiently deposit their energy and the neutron yield remains low. In future work, we will achieve the higher core density (>10 g/cm^{3}); then hot electrons could contribute more to the core heating via drag heating. Together with hot electrons, the ion contribution to fast ignition is indispensable for realizing high-gain fusion. By virtue of its core heating and ignition, the proposed scheme can potentially achieve high gain fusion.

The efficacy of calcineurin inhibitors for the treatment of interstitial lung disease associated with polymyositis/dermatomyositis.

Interstitial lung disease (ILD) in patients with polymyositis (PM) and dermatomyositis (DM) is often resistant to treatment and life threatening, being recognized as one of the severest complication in these autoimmune disorders. Patients with clinically amyopathic dermatomyositis (CADM) or those with anti-CADM140/MDA5 antibody are especially prone to develop rapidly progressive interstitial pneumonia. We retrospectively analyzed 46 patients with PM/DM admitted to our hospital and identified DM, rapidly progressive disease, honeycomb lung, CADM and extensive ILD as risk factors for recurrence or death. In the presence of two or more risk factors, the sensitivity and specificity for the prediction of death or relapse were 81.3% and 76.7%, respectively. Calcineurin inhibitors have been widely used as induction and maintenance therapy for PM/DM-associated ILD. Recently we reported the benefit of tacrolimus on the disease-free survival and event-free survival of the patients with PM/DM-associated ILD. Among those patients treated with tacrolimus, poor prognostic factors for death, recurrence or severe adverse event were identified as acute progression of the disease, honeycomb lung, forced vital capacity (FVC) less than 80% and having DM. The potential effectiveness of an intensive therapy protocol with triple therapy that comprises high-dose corticosteroids, calcineurin inhibitors and cyclophosphamide has been reported.

Long-term outcome in Japanese patients with lupus nephritis.

The objective of this study was to clarify the long-term outcome in patients with lupus nephritis (LN) according to the International Society of Nephrology and Renal Pathology Society classification. This retrospective analysis comprised 186 Japanese patients given a diagnosis of LN by renal specimen with a mean observation period of 12 years. Primary end point was defined as death or end-stage renal disease, and standardized mortality ratios were calculated. Five patients presented with histopathological class I, 62 with II, 21 with III or III+V, 73 with IV or IV+V and 25 with V. Fourteen deaths occurred, corresponding to an overall standardized mortality ratio of 3.59 (95% confidence interval 2.02-5.81, p < 0.0001). Kaplan-Meier analysis revealed a 10-year overall survival of 95.7%. Nephrotic proteinuria (≥3.5 g/day) at baseline was identified as an independent poor prognostic factor for overall survival in Cox regression analysis. Kaplan-Meier analysis revealed a 10-year renal survival as 94.3%. Male gender and nephrotic proteinuria at baseline were identified as independent poor prognostic factors for renal survival in Cox regression analysis. In conclusion, LN was associated with a 3.59-fold increase in mortality compared with the general population. Male gender and nephrotic proteinuria were predictive for poor renal outcome.

Management of a primary retroperitoneal mucinous cystadenocarcinoma: case report.

PURPOSE: To review the treatment of primary retroperitoneal mucinous cystadenocarcinoma (PRMC). CASE REPORT: A 30-year-old woman had a large retroperitoneal mucinous adenocarcinoma treated with conservative laparoscopic surgery. Two years later, she was found to have bilateral ovarian cysts at the time of cesarean section. Since cystectomies revealed mucinous adenocarcinoma, she underwent complete surgical staging and adjuvant chemotherapy at this time. CONCLUSION: A rare case of similar cancer in the ovary following treatment for PRMC was described. It is unclear whether the prognosis is improved by oophorectomy. Further cases and long-term follow-up are necessary.

Influence of cardiac output on the pseudo-steady state remifentanil and propofol concentrations in swine.

BACKGROUND: The propofol concentration during constant infusion is affected by a change in cardiac output, but the effect of this change on remifentanil, which is frequently used in combination with propofol, is unclear. METHODS: Ten swine were anaesthetised through inhalation of isoflurane and maintained with 1.5% isoflurane. After infusion of remifentanil (0.5 µg/kg/min) and propofol (6 mg/kg/h after 2 mg/kg bolus infusion) for 60 min (baseline 1), cardiac output was increased by continuous infusion of dobutamine and termination of isoflurane (high cardiac output state). Dobutamine infusion was then stopped, 1.5% isoflurane was restarted, and cardiac output was allowed to return to baseline (baseline 2). Finally, cardiac output was decreased by administration of 3% isoflurane (low cardiac output state). Blood samples were collected from the femoral artery at 10, 30, and 60 min after the change to each haemodynamic state. RESULTS: An inverse relationship was found between cardiac output and the plasma remifentanil and propofol concentrations. The plasma drug concentrations were given by the following equations: [remifentanil] (ng/ml) = 17.5/cardiac output (l/min) + 4.52; and [propofol] (µg/ml) = 3.34/cardiac output + 1.17. The influence of changes in cardiac output on remifentanil were similar to those for coadministered propofol and the influence on the concentration of each drug was greater with decreasing cardiac output. CONCLUSIONS: The plasma remifentanil concentration is influenced by cardiac output in a similar manner to that of propofol during remifentanil and propofol anaesthesia, although the metabolic sites are different.

Fusion using fast heating of a compactly imploded CD core.

A compact fast core heating experiment is described. A 4-J 0.4-ns output of a laser-diode-pumped high-repetition laser HAMA is divided into four beams, two of which counterilluminate double-deuterated polystyrene foils separated by 100 µm for implosion. The remaining two beams, compressed to 110 fs for fast heating, illuminate the same paths. Hot electrons produced by the heating pulses heat the imploded core, emitting x-ray radiations >20 eV and yielding some 10(3) thermal neutrons.

Influence of haemorrhage on the pseudo-steady-state remifentanil concentration in a swine model: a comparison with propofol and the effect of haemorrhagic shock stage.

BACKGROUND: The increase in remifentanil concentration during haemorrhagic shock and the difference between this effect and that for propofol are not fully understood. We investigated the influence of haemorrhage on the pseudo-steady-state remifentanil concentration in a porcine model and compared the changes with those for propofol. METHODS: After infusion of remifentanil (0.5 µg kg⁻¹ min⁻¹) and propofol (6 mg kg⁻¹ h⁻¹ after 2 mg kg⁻¹ bolus infusion) for 60 min, nine swine [mean (standard deviation) body weight=26.3 (1.3) kg] were studied using a stepwise haemorrhage model (10% of estimated blood volume removed every 30 min until 1.5 h, and stepwise removal of 5% every 30 min thereafter until circulatory collapse). Haemodynamic and metabolic variables and plasma remifentanil and propofol concentrations were measured at every step. RESULTS: A mean volume of 913 (82) ml of blood was drained before reaching circulatory collapse. The increases in plasma concentrations from the prehaemorrhagic value fitted the following equations: % increase in remifentanil=2.1 × cumulative blood loss (% of initial blood volume) and % increase in propofol = 0.7 × cumulative blood loss during compensated shock; and % increase in remifentanil = 27.4 × cumulative blood loss-897 and % increase in propofol = 9.5 × cumulative blood loss-306 during uncompensated shock. Remifentanil concentrations were highly correlated with the reciprocal of cardiac output. CONCLUSIONS: During haemorrhage, the plasma remifentanil concentration showed a three-fold greater increase than that of propofol in administration by continuous infusion.

Isotype-specific immunoregulation. Evidence for a distinct subset of T contrasuppressor cells for IgA responses in murine Peyer's patches.

The ability of murine Peyer's patch (PP) T contrasuppressor cells (Tcs) to reverse oral tolerance to the T cell-dependent (TD) antigen SRBC was studied both in vivo and in vitro. C3H/HeJ mice given SRBC orally for 4 wk are not rendered tolerant to this antigen and were used as a source of PP Tcs cells for adoptive transfer to identically treated, orally tolerized C3H/HeN mice. Transfer of 10(4) or 5 X 10(4) V. villosa-adherent PP T cells resulted in splenic IgM, IgG, and mainly IgA responses in C3H/HeN mice challenged systemically with SRBC. The T cell responsible was Lyt-1+, 2-, L3T4-, I-JK+ and V. villosa lectin-adherent, all characteristics of mature effector Tcs cells. This C3H/HeJ PP Tcs cell subset was also effective when added to in vitro cultures of tolerized spleen cells derived from SRBC-fed, C3H/HeN mice. Interestingly, C3H/HeJ PP Tcs cells restored mainly IgA responses when transferred in vivo or when added to suppressed C3H/HeN splenic cultures. Comparison of the functional activity of Tcs cells derived from spleen or PP of orally immunized C3H/HeJ mice revealed that splenic Tcs cells supported responses of all 3 isotypes; however, PP Tcs cells yielded three-fourfold higher IgA responses, when compared with IgM or IgG anti-SRBC responses. Adherence of C3H/HeJ PP Tcs to an Fc alpha R+ T cell line derived from IgA-specific Th cells resulted in a nonadherent cell fraction that potentiated only IgM and IgG responses, while bound Tcs cells preferentially supported IgA responses. These results suggest that murine PP contain IgA-specific Tcs cells that allow IgA response induction in the presence of Ts cells that mediate oral tolerance.

Surgical treatment of labyrinthine fistula in patients with cholesteatoma.

Labyrinthine fistula is one of the most common complications of chronic otitis media associated with cholesteatoma. The optimal management of labyrinthine fistula, however, remains controversial. Between 1995 and 2005, labyrinthine fistulae were detected in 31 (6 per cent) patients in our institution. The canal wall down technique was used in 27 (87 per cent) patients. The cholesteatoma matrix was completely removed in the first stage in all patients. Bone dust and/or temporalis fascia was inserted to seal the fistula in 29 (94 per cent) patients. A post-operative hearing test was undertaken in 27 patients; seven (26 per cent) patients showed improved hearing, 17 (63 per cent) showed no change and three (11 per cent) showed a deterioration. The study findings indicate that there are various treatment strategies available for cholesteatoma, and that the treatment choice should be based on such criteria as auditory and vestibular function, the surgeon's ability and experience, and the location and size of the fistula.

Superselective, intra-arterial, rapid infusion chemotherapy for external auditory canal carcinoma.

Previously, the treatment of carcinoma of the external auditory canal has mainly involved surgical resection. In order to enable organ preservation and to obtain cancer-free surgical margins, we introduced the use of superselective, intra-arterial, rapid infusion chemotherapy combined with radiotherapy to treat this condition.We reviewed our patients' tumour stages, feeding arteries and clinical outcomes. Tumours were staged according to the Pittsburgh staging system. Chemotherapy was administered intra-arterially in the angiography suite via transfemoral catheterisation of the feeding arteries. Four patients underwent superselective, intra-arterial, rapid infusion chemo-radiotherapy. A complete response was obtained in all four patients. The overall toxic side effects were modest.Superselective, intra-arterial, rapid infusion chemotherapy can be an effective, organ-preserving treatment for external auditory canal carcinoma, with a high cure rate.

Effect of tympanic membrane perforation on middle-ear sound transmission.

Tympanic membrane perforation causes a sound conduction disturbance, and the size of this conduction disturbance is proportional to the perforation area. However, precise evaluation of perforation size is difficult, and there are few detailed reports addressing this issue. Furthermore, such evaluation becomes more difficult for irregularly shaped perforations. This study conducted a quantitative evaluation of tympanic membrane perforations, using image analysis equipment.A significant correlation was found between the degree of sound conduction disturbance and the perforation area; this correlation was greater at low frequencies following a traumatic perforation. The conductive disturbance associated with chronic otitis media was significantly greater at low frequencies. Circular perforations caused only minor conduction disturbance. Perforations in the anteroinferior quadrant were associated with greater conduction disturbance. Traumatic spindle-shaped perforations and malleolar perforations were associated with greater conduction disturbance.

Analysis of surgical treatment for middle-ear cholesterol granuloma.

Cholesterol granuloma is an intractable ear disease. Many studies of this condition have been published since the initial report by Manasse. However, the pathogenesis of this condition is unclear. This study reviewed the treatment of middle-ear cholesterol granuloma in 16 patients undergoing surgical treatment at Kurume University Hospital.The relationship between patients' pre-operative tympanic membrane findings and post-operative course was analysed. Patients with swollen tympanic membranes had significantly poorer outcomes. Patients with retracted tympanic membranes and those undergoing ossicular chain reconstruction had significantly better outcomes. The patients' overall hearing success rate at approximately two weeks post-operatively was 75 per cent. However, by six months post-operatively, the overall hearing success rate had declined to 62.5 per cent. Patients with poor hearing two weeks post-operatively did not acquire better hearing.

New silicone tube placement therapy for patients with an anterior glottic web.

An anterior glottic web in adults comprises a bridge of scar tissue commonly formed as a result of iatrogenic laryngeal injury. Traditionally, procedures such as transcervical midline thyrotomy and keel placement have been used to repair this condition. However, we recently repaired an anterior glottic web using a new surgical procedure involving a silicone tube instead of a keel. We herein report this case, in which we placed a silicone tube at the anterior commissure after resection of an anterior glottic web, under endolaryngeal microsurgery, without performing a tracheostomy.

Salvage surgery for a locally persistent or recurrent tumour in maxillary cancer patients who have undergone radiotherapy and concomitant intra-arterial cisplatin: implications for surgical margin assessment.

Limited information about salvage surgery is available for locally persistent and recurrent maxillary sinus cancers after the completion of chemoradiation therapy. Seventy-six maxillary sinus cancer patients who had undergone chemoradioselection using initial radiotherapy and concomitant intra-arterial cisplatin were screened retrospectively. Twenty-four of these patients who had a locally persistent or recurrent tumour were investigated. The 2-year overall survival rate of patients with maxillary sinus cancer of all types was 39.0% for those who underwent salvage surgery and 10.0% for those who did not. The 2-year overall survival rate of patients with maxillary sinus squamous cell carcinoma was 45.8% for those who underwent salvage surgery and 11.1% for those who did not. Furthermore, the 2-year local control and overall survival rates of patients with positive and negative surgical margins were 14.3% and 83.3% and 14.3% and 66.7%, respectively. There were significant differences in local control (P=0.004) and overall survival (P=0.005) regarding surgical margin status. Although salvage surgery for a locally persistent or recurrent maxillary sinus cancer is a feasible treatment, patients with positive surgical margins are more prone to local relapse. Therefore, surgical safety margins should be assessed thoroughly.

Lipophilic beta-adrenoceptor antagonist propranolol increases the hypnotic and anti-nociceptive effects of isoflurane in a swine model.

BACKGROUND: We have previously reported that landiolol, an ultra-short-acting beta1-adrenoceptor antagonist, does not alter the anaesthetic effects of isoflurane. Here, we investigated the influence of propranolol on the electroencephalographic (EEG) effects and minimum alveolar concentration (MAC) of isoflurane. METHODS: Fourteen swine [25.0 (SD 4.0) kg] were anaesthetized by isoflurane inhalation. The inhalation concentration was decreased to 0.5% and maintained for 25 min, before being returned to 2%, and maintained for a further 25 min. End-tidal isoflurane concentrations and spectral edge frequencies were recorded. Pharmacodynamic analysis was performed using a sigmoidal inhibitory maximal effect model for spectral edge frequency vs effect-site concentration. After measurement of the EEG effect, MAC was determined using the dew-claw clamp technique, in which movement in response to clamping is recorded. After completion of control measurements, a propranolol 4 mg bolus followed by an infusion (2 mg h(-1)) was started. After a 30 min stabilization period, the inhalation concentration of isoflurane was varied as in the control period and MAC was re-assessed. RESULTS: Propranolol shifted the concentration-effect relationship to the left and decreased the effect-site concentration that produced 50% of the maximal effect from 1.30 (0.18) to 1.13 (0.17)%. Propranolol also decreased isoflurane MAC from 1.91 (0.35) to 1.54 (0.32)%. CONCLUSIONS: Propranolol alters both the hypnotic and anti-nociceptive effects of isoflurane. In contrast to landiolol, lipophilic beta-adrenoceptor antagonists may increase the potency of inhalational anaesthetics.

Do the kidneys contribute to propofol elimination?

BACKGROUND: Propofol is mainly metabolized in the liver, but extrahepatic clearance may also be important since systemic propofol clearance exceeds hepatic clearance. Recent reports suggest that the kidneys contribute to propofol elimination in humans and here we investigated renal elimination of propofol in a controlled animal study. METHODS: Seventeen swine were anaesthetized with 5% isoflurane induction and 2% isoflurane maintenance. After a left subcostal incision, the left kidney and renal pedicle were exposed by an approach via the retroperitoneum and the renal vein was identified for blood sampling. Propofol was then administered via the right jugular vein at a rate of 2 mg kg(-1) h(-1). After 120 min of pseudo-steady-state infusion of propofol (Baseline 1), cardiac output (CO) was increased by continuous infusion of dobutamine for 30 min (high-CO state). Thirty minutes after stopping dobutamine (Baseline 2), CO was decreased by bolus administration of propranolol (low-CO state). Blood samples were collected simultaneously from the renal vein (direct puncture) and the femoral artery at Baseline 1, in the high-CO state, at Baseline 2, and in the low-CO state. RESULTS: There was no significant difference in propofol concentration between femoral arterial and renal venous blood in all states. The propofol concentration significantly decreased with increased CO, but renal extraction was not observed in any state. CONCLUSIONS: The kidneys are a minor site of propofol elimination in a swine model.

Efficacy of a skin-protection powder for use as a dressing for intractable ulcers.

OBJECTIVE: Stomahesive skin-protection powder has been reported to be useful as a skin-care and skin-barrier product for the management of stomas. This study aimed to evaluate its efficacy, in terms of wound healing, moisture retention and pain management, as an alternative to conventional dressing materials. Both clinical and animal studies were undertaken. METHOD: The efficacy of the Stomahesive powder was tested by measuring the thickness of granulation tissue formed in a total skin defect in a db/db mouse model. We then compared the healing process using either the skin-protection powder or a conventional film dressing material. In the clinical study 17 patients with various intractable ulcers were treated with Stomahesive powder, and healing was evaluated. RESULTS: In the mouse model, granulation tissue in the wounds treated with the powder was 2.86 times thicker than that of the wounds treated with the film dressing. In the clinical study, 16 out of 17 wounds healed completely. CONCLUSION: The Stomahesive powder could be an effective treatment modality for contact ulceration, superficial ulcers with complex contours and morphology, and superficial ulcers contaminated by liquid faeces or vaginal discharge that have not responded to conventional dressings. DECLARATION OF INTEREST: None.