Influence of using history of immune checkpoint inhibitor therapy for neutropenia caused by combination therapy of ramucirumab and docetaxel.

Recently, pretreatment with immune checkpoint inhibitors (ICIs) has been shown to enhance the therapeutic effects of the combination therapy of ramucirumab (RAM) and docetaxel (DTX); however, its influence on the drug's side effects remains unclear. This study investigated the influence of pretreatment with ICIs on the incidence of neutropenia caused by RAM + DTX therapy in patients with non-small cell lung cancer (NSCLC). Patients with NSCLC who received RAM + DTX therapy at Gifu Prefectural General Medical Center between April 2016 and December 2020 were enrolled. Retrospective data regarding age, sex, performance status and detailed treatment history, among others, at treatment initiation were collected from the patients' electronic medical records. Additionally, data on the course number of RAM + DTX therapy, supportive therapy and blood biochemical parameters, including leukocyte and neutrocyte counts, during the treatment period were collected. We identified 41 patients receiving RAM + DTX therapy. Among the more than grade 3 adverse events caused by this therapy, neutropenia was the most common (78.1%). Despite the fact that all previous risk factors influencing this incidence rate had corresponded, the only factor influencing the incidence rate of neutropenia more than grade 3 was ICI treatment history. A difference in the incidence of neutropenia more than grade 3 in the Kaplan-Meier curve was observed between patients with and without ICI pretreatment history (p = 0.037). The pretreatment history of ICI therapy affects the incidence of neutropenia caused by RAM + DTX therapy in patients with NSCLC.

Comparison of specificities between two interferon-gamma release assays in Japan.

We compared the specificities of two interferon-gamma release assays (IGRAs), T-SPOT®.TB (T-SPOT) and the QuantiFERON®-TB Gold In-Tube (QFT-GIT) assay, in strictly selected subjects with a low risk of tuberculosis (TB) infection in a Japanese population. Of 111 subjects who were mostly bacille Calmette-Guérin vaccinated, one was positive using both assays and 110 were negative, using international cut-off values. Although several meta-analyses report that QFT-GIT has higher specificity than T-SPOT, our study demonstrates that the specificity of both assays is equally high in a population with a truly low risk of TB infection.

Use of the QuantiFERON-TB Gold test for screening tuberculosis contacts and predicting active disease.

OBJECTIVE: To evaluate the performance of the QuantiFERON(R)-TB Gold (QFT-G) test for screening tuberculosis (TB) contacts and estimating their risk of progressing to active TB disease. METHODS: Data on clinical progression to active disease were collected from public health centres 2 years after close contacts of TB cases had been QFT-G-tested. RESULTS: Among 3102 contacts observed, 419 were QFT-G-positive, and isoniazid (INH) treatment was initiated in 323. Twenty (4.8%) of these 419 developed TB disease. Among 2683 QFT-G-negative persons, 19 were diagnosed with TB (0.7%) during the average follow-up period of 1.6 years. The estimated sensitivity of QFT-G in detecting contacts who would progress to active TB was 51%, or 64% allowing for the effects of INH treatment. Among the QFT-G-negative contacts, all those who developed TB disease were contacts of highly infectious cases. Large-scale tuberculin skin testing was not available. CONCLUSIONS: TB incidence among QFT-G-positive contacts was higher than among QFT-G-negative contacts, but the number of TB cases among QFT-G-negative contacts is non-negligible, especially among contacts of highly infectious cases.

Spin transition in a four-coordinate iron oxide.

Spin transition has attracted the interest of researchers in various fields since the early 1930s, with thousands of examples now recognized, including those in minerals and biomolecules. However, so far the metal centres in which it has been found to occur are almost always octahedral six-coordinate 3d(4) to 3d(7) metals, such as Fe(II). A five-coordinate centre is only rarely seen. Here we report that under pressure SrFe(II)O(2), which features a four-fold square-planar coordination, exhibits a transition from high spin (S = 2) to intermediate spin (S = 1). This is accompanied by a transition from an antiferromagnetic insulating state to a ferromagnetic so-called half-metallic state: only half of the spin-down (d(xz),d(yz)) states are filled. These results highlight the square-planar coordinated iron oxides as a new class of magnetic and electric materials.

Waning of the specific interferon-gamma response after years of tuberculosis infection.

HYPOTHESIS: Memory T-cell responses to specific antigens wane over time in subjects with tuberculosis (TB) infection. SETTING: Accumulated evidence indicates that QuantiFERON-TB Gold (QFT-G), a specific whole-blood interferon-gamma (IFN-gamma) based assay, can detect recent TB infections with superior sensitivity and specificity. OBJECTIVE: We applied this technique to the adult population of a Japanese community to determine its epidemiological usefulness. METHOD: A total of 1559 subjects attending periodic health screening volunteered to participate in the study. RESULTS: The QFT-G positive rates were 3.1% for those aged 40-49 years, 5.9% for those aged 50-59 and 9.8% for those aged 60-69. The expected infection prevalence estimated by the authors from a series of studies was 11.1%, 29.6% and 53.1% for those aged 40-49, 50-59 and 60-69 years, respectively. This wide gap between the expected and observed positivity suggests that the IFN-gamma response waned substantially with time after infection. Those with X-rays suggestive of old TB lesions exhibited positivity rates well below 100%. CONCLUSION: The specific IFN-gamma response may wane considerably with time after infection. Longitudinal studies are required to investigate long-term dynamics of cell-mediated immunity in infected donors.

Altered expression of genes in experimentally induced myopic chick eyes.

PURPOSE: To identify a casual pathway between the alteration in visual experience, due to form deprivation and hyperopic defocus, and the increase in eye growth, we searched for candidate genes having regulatory effects on eye growth under myopic conditions. METHODS: The expression of the brain-derived neurotrophic factor, neurotrophin-3, sonic hedgehog, nerve growth factor, Six-3 and the Lh-2 group of genes in the transcriptional level after experimentally induced myopia (form-deprivation by goggles and by hyperopic defocus using negative spectacle lenses) were evaluated by semiquantitative reverse transcriptional polymerase chain reaction and Northern blot analysis. RESULTS: Results showed that only the sonic hedgehog gene was differentially expressed in the experimentally induced myopic retinal samples compared with controls. CONCLUSIONS: The sonic hedgehog gene may have regulatory functions in the signaling of the cascade of events that leads to axial elongation and vitreous enlargement of the eye under myopic conditions.

Expression of Sonic hedgehog and retinal opsin genes in experimentally-induced myopic chick eyes.

The purpose of this study was to evaluate changes in the expression of different genes in chick retinal tissues after induction of experimental myopia and to evaluate the roles of these genes in the regulation of postnatal eye growth and myopia. Form-deprivation using occlusive goggles and hyperopic defocus by negative spectacle lenses were used to induce myopia in hatched chicks. Expression levels of Sonic hedgehog, its receptor complex, and other retinal cell genes were evaluated by semi-quantitative reverse transcription-polymerase chain reaction. Levels of Sonic hedgehog protein were further evaluated by Western blot analysis. The induction of myopia caused significant increase in expression of Sonic hedgehog mRNA and protein and increased expression of blue and red opsin mRNA. In contrast, the expression of mRNA for Sonic hedgehog receptor complex (Patched-Smoothened), rhodopsin, vimentin, green opsin, violet opsin, and HPC-1 were unaffected by the induction of myopia. The increase in expression of Sonic hedgehog in chick retinas in experimentally-induced myopia suggests involvement in the retina control of postnatal eye growth. Furthermore, Sonic hedgehog may influence the expression of blue and red opsins under myopic conditions.

Differential expression of neuroendocrine-specific protein in form-deprived chick eyes.

PURPOSE: To identify genes that are highly expressed in form-deprived retina-retinal pigment epithelium-choroid tissues. Neuroendocrine-specific proteins were found to be highly expressed. METHODS: mRNAs enriched in retina-retinal pigment epithelium-choroid tissues from 3-, 7-, and 14-day form-deprived chick eyes were isolated by differential display technique with cDNA library screening. Neuroendocrine-specific protein A and C were cloned in control and form-deprived eyes. mRNA and protein levels, with respective regional localizations, were examined by Northern blot, Western blot, and immunohistochemical analyses, respectively. RESULTS: The isolated clone included an insert with a sequence homologous to both chick neuroendocrine-specific proteins A and C. The increases in mRNA and protein levels were confirmed by Northern and Western blot analyses, respectively. Immunohistochemical localization of neuroendocrine-specific proteins A and C was detected in the layer of photoreceptor inner segments, presumably in the cone cells. Northern blot analysis using negative lenses showed that levels of neuroendocrine-specific protein A and C mRNAs were not altered using negative lenses. CONCLUSIONS: The expression of both neuroendocrine-specific proteins A and C mRNAs in cone photoreceptor cells was upregulated within 14 days of form deprivation, but not in response to negative spectacle lenses. These data suggest that the increase in induction of neuroendocrine-specific proteins is not a secondary consequence of ocular elongation or myopic refraction. Induction of neuroendocrine-specific proteins in form-deprived eyes may be causally related to the development of myopia or may be an unrelated effect of form deprivation.

Up-regulation of crystallin mRNAs in form-deprived chick eyes.

Form-deprivation of chicks during early postnatal development results in ocular enlargement and great myopic refractive error (form-deprivation myopia). Previous studies have indicated that the retina, RPE and choroid play important roles in ocular enlargement in form-deprivation myopia. We aimed to isolate genes up-regulated in the retina-RPE-choroid of form-deprived chick eyes. A suppression subtractive hybridization method was used to compare mRNA expression in the retina-RPE-choroid of form-deprived and control eyes. One up-regulated cDNA was isolated and identified as part of chick delta1-crystallin cDNA. Northern blot and RT-PCR analyses demonstrated that delta1-crystallin mRNA was up-regulated in the retina-RPE at day 7 after form-deprivation treatment. Semi-quantitative RT-PCE analysis of the expression of several transcription factors indicated that Sox1 and Sox3 were upregulated in parallel with delta1-crystallin mRNA in form-deprived eyes. Northern blot analysis demonstrated that alphaA-, betaA3/A1-, betaB1-, and betaB2-crystallin mRNAs were also up-regulated in form-deprived eyes. Although the detailed mechanisms and functions of the crystallin family genes in the retina-RPE-choroid of form-deprived eyes remain unclear, results of our study suggests that form-deprivation affects the expression of these genes in chick eyes.

Evaluation of the therapeutic effect of radiotherapy on cervical cancer using magnetic resonance imaging.

PURPOSE: This study was performed to evaluate magnetic resonance imaging (MRI) in determining the therapeutic effect of radiotherapy (RT) on cervical cancer. METHODS AND MATERIALS: Serial MRI studies were performed in 42 patients with predominantly advanced cervical cancer before, during, and after radiotherapy. Patients underwent external irradiation combined with high-dose-rate intracavitary (HDR) brachytherapy. T-2 weighted spin-echo pulse sequences with long repetition and echo times were used at a field strength of 1.5 T. Multiple punch biopsies of the cervix were obtained from the high-signal intensity area in all patients at the same time as the MRI. RESULT: In biopsies performed immediately after RT, no residual tumors were found in 36 patients (86%); in 6 patients, residual tumors were observed. The simultaneous MRI study demonstrated no high-signal intensity on T2-weighted images in 28 patients. A high-signal area was observed in 14 patients, and this disappeared 3 months after RT in 8 patients with a negative histological study. The sensitivity, specificity, and accuracy of MRI studies at 3 months after RT were 100%. When the relationship between reduction of tumor volume at 30 Gy and local tumor control was analyzed, every patient with a reduction under 30% gained local control. Also, patients with no residual tumors 3 months after RT gained local control. CONCLUSION: MRI studies performed at 30 Gy of external irradiation and 3 months after RT were predictive factors of local control.

[Effect of low-dose sulpiride on dopamine metabolism in rat nucleus accumbens and locomotor activity: studies with intracerebral dialysis].

Changes in the concentration of dopamine (DA) and its metabolites, 3, 4-dihydroxyphenyl-acetic acid (DOPAC) and homovanillic acid (HVA), were determined sequentially in freely moving rats by using a brain dialysis method. The purpose of this study was to investigate the relationship between changes in the dopamine metabolism in the nucleus accumbens and locomotor activities following low-dose (5 mg/kg) sulpiride administration. The DA content in the dialysis fluid rose significantly 4 to 6 h after sulpiride administration. The DOPAC content rose significantly 6 h after sulpiride administration. The HVA content did not show a significant change. A slight increase of locomotor activity was found, but it was not statistically significant. The elevation of DA release in nucleus accumbens by sulpiride might relate to the clinical efficacy of low-dose administration of this drug for mood disorders.

Development of grating acuity in infants with Retinopathy of Prematurity.

PURPOSE: To evaluate the visual development in infants with stage 1 approximately 3 ROP and compare their visual results with healthy preterm infants. PATIENTS AND METHODS: One hundred forty-four premature infants were recruited and were divided into 3 groups according to the stage of ROP. Randomly selected preterm subjects with no ROP were taken as controls. Ophthalmic examinations started 4 to 7 weeks after birth and were repeated as needed until the retina was fully vascularized or until any ROP that developed had resolved. Grating acuity was measured by acuity cards between 35-45 weeks of corrected age and by PL method at 12, 18 and 24 months of age. RESULTS: Infants with stage 3 ROP had slightly lower visual acuity scores compared to other infants at most of the testing points throughout the 35-45 week period, which did not show statistical significance at any week. Infants with stage 2 and 3 ROP had similar visual acuity values but slightly lower acuity scores than infants with stage I or no ROP at the 12 month follow-up. The differences were not statistically significant. Stage 3 ROP infants had significantly lower acuity scores compared to infants with stage 1-2 or no ROP at the 18 and 24 month follow-up visits (p<0.0001). CONCLUSION: We stress periodic monitoring of early visual acuity in infants with ROP because of the possibility of impaired visual development.

[Roles of outpatient nurses in the care of cancer patients receiving MS Contin tablets].

Pain relief is very important to improve the QOL of cancer patients. Accurate pain assessment and offering suitable drug information on MS Contin tablets (MSC) are important roles of outpatient nurses for the effective use of MSC. We examined the present status of symptom relief among cancer outpatients and from this discuss the practice of outpatient nursing. Forty-eight outpatients receiving MSC were interviewed by mail with regard to pain relief, the side effects of MSC, and the drug information they had been provided. Cancer pain was well controlled in 68% of outpatients by MSC, but MSC was not effective in 13%. Some side effects were observed in 68% of patients, 10% of which were poorly controlled. Sixty-five percent of patients were informed about MSC, but only 47% were informed about measures against these side effects. The following conclusions were reached: 1) MSC should be explained individually and repeatedly, 2) exact informations on a patient's status should be collected using scales and charts, 3) nurse charts should record when MSC is initially administered and when the dosage is changed, and 4) the cases of poorly controlled patients should be studied and specialists consulted if necessary.

[Radiotherapy for carcinoma of the buccal mucosa: analysis of prognostic factors].

The radiotherapeutic results of 55 patients with carcinoma of the buccal mucosa were analyzed to determine the prognostic factors and appropriate treatment modality. They were classified into 5 groups according to treatment modality: group A (preoperative radiotherapy followed by surgery), group B (interstitial implant), group C (electron therapy), group D (mainly external radiotherapy) and group E (external radiotherapy followed by mold therapy with remote afterloading system). The overall 5-year survival rates for groups A, B, C, D, E and the entire group were 50%, 61%, 67%, 29%, 25% and 48%, respectively. The cumulative 5-year local control rates for groups A through E were 81%, 94%, 75%, 33% and 25%, respectively. In univariate analysis, T stage (T1-2 vs. T3-4), N stage (N0 vs. N1-3), clinical stage (II vs. III-IV), histologic grade (well differentiated vs. moderately and poorly differentiated) and treatment modality (A-C vs. D-E) were significantly related to overall survival (p < 0.05). Multivariate analysis revealed that treatment modality (groups A-C) and N0 stage were significantly associated with favorable prognosis (p < 0.05). These results suggest that interstitial implants are comparable with surgery for T1 to early T3 lesions, with or without slight invasion to the bucco-alveolar sulci or retromolar areas, that can be treated with a single-plane implant.

Visual function following congenital cataract surgery.

To evaluate the results of congenital cataract extraction and postoperative visual function, we retrospectively reviewed the records of 95 patients who underwent pars plana (plicata) lensectomy or aspiration surgery. Forty-nine percent of the patients with bilateral aphakia and 25% with bilateral pseudophakia had a Landolt visual acuity of 0.5 or above at the final visit. The figures were 31% and 66% for patients with unilateral aphakia and pseudophakia, respectively. Eight patients (16.3%) with bilateral and 2 patients (5.8%) with unilateral cataract for whom contact lenses were prescribed after surgery attained fine stereopsis. Five of 8 patients (62.5%) with unilateral cataract who had intraocular lens implantation ended up with gross or fine stereopsis. We stress that very early surgery and optical correction in the sensitive period of binocular visual development should be instituted, especially in the presence of dense opacities. A good postoperative visual outcome can be achieved in patients undergoing late surgery if the opacities are light or partial in nature. We also reemphasize the importance of aggressive and diligent visual rehabilitation and occlusion therapy against amblyopia.

Differential expression of nitric oxide synthase isoforms in form-deprived chick eyes.

PURPOSE: To clarify whether nitric oxide synthase (NOS) is involved in development of myopia, we examined the influence of form deprivation on the expressions of NOS isoform mRNA. METHODS: NOS isoform cDNAs were amplified from total RNA extracted from control and 7-day-form-deprived chick retina-RPE (retinal pigment epithelium)-choroid, using competitive RT-PCR (reverse-transcription polymerase chain reaction). Each NOS isoform protein was also analyzed by Western blotting and immunohistochemistry. RESULT: Expression of inducible NOS (iNOS) mRNA was highest in the control chick retina-RPE-choroid, followed by the expression of brain NOS (bNOS) mRNA. Expression of endothelial NOS (eNOS) mRNA was faint. The iNOS protein level, however, was only slightly higher than the levels of the bNOS and eNOS proteins and was found mainly in the outer part of the photoreceptor layer and inner and outer parts of RPE and choroid. bNOS alone was found in the outer nuclear layer. Although form deprivation reduced the iNOS and bNOS mRNA expressions, only the iNOS protein showed significant reduction. CONCLUSION: All three NOS isoforms were expressed in chick retina-RPE-choroid. Predominant expression of iNOS, instead of bNOS and eNOS, suggested the existence of ocular tissue-specific regulation of the iNOS gene. In addition to differences in expression level, bNOS displayed regional differential expression. Moreover, only iNOS was reduced in response to form deprivation. It is suggested that NOS isoforms may be differentially involved in the mechanisms regulating the posterior eye tissues, including myopic eye growth.

[Terminal care of the cancer patient at home--patient and family spending the last moments together].

Some 129 cancer patients were taken care of at home by the visiting nurse team of our hospital since 1994 to 1997; 116 patients have already died, 50 of them at home (group A), and 66 at the hospital (group B). We analyze the differences the between two groups in nutritional assistance, pain control and manpower in looking after a patient. Twice as many patients in group A took nutritional medication (drip infusion or intravenous hyperalimentation, for example) than group B. More patients in group A used oral and suppository morphine than group B. In group A 70% of patients (56% in group B) had more than two persons looking after at home. The important factors for a good recuperation at home are: 1. Available nutritional assist available. 2. Good control. 3. Less burden and anxiety of the person looked after. To spend pain desirable last moments together, it is important for the visiting nurse team to take proper care and to confirm the wishes of the patient and family, considering the rapidly changing conditions of the individual patient.

Thallium-201 single-photon emission tomography in the treatment follow-up of nasopharyngeal carcinoma.

In order to assess the usefulness of thallium-201 single-photon emission tomography (SPET) in the treatment follow-up of nasopharyngeal carcinoma (NPC), a total of 75 201T1 SPET studies were performed in 18 patients with histologically proven NPC. The findings were compared with those of magnetic resonance imaging (MRI) before and after therapy. Four patients received radiotherapy alone while the other 14 received concurrent chemo-radiotherapy. Treatment response was classified as complete (CR) or partial (PR) based on the findings of MRI and 201T1 SPET. Intense 201T1 uptake by the tumour was seen in all 18 patients before treatment. After treatment, MRI showed seven CRs and 11 PRs, whereas 201T1 SPET showed 13 CRs and five PRs. In 12 patients, the results of 201T1 SPET were in agreement with those of MRI. In six patients MRI showed PR but 201T1 showed CR. Follow-up (mean 10.6 months) MRI and 201T1 SPET studies of these six patients revealed that tumour gradually decreased and finally vanished in three patients. This preliminary study indicates that 201T1 SPET has potential in the assessment of early response to treatment of patients with NPC when compared with MRI.

[Evaluation by visiting nurse in end-stage cancers--family questionnaire for patients who died after visiting nurse].

Since April 1994, we have provided visiting nurse care for patients with end-stage of cancers. A questionnaire was sent to 72 families of patients who died of cancer and who received after visiting nurse care. The response rate to the questionnaire was 76.4% (55 patients). One group of 27 patients died at home (Group A), and the other group of 28 patients died in the hospital (Group B). Patients who knew they had cancer accounted for 85.2% in Group A, and 57.1% in Group B. Of all patients, 69.1% desired home nursing, with 77.8% in Group A, and 60.7% in Group B. The satisfaction of families with the visiting nurse was evaluated. In Group A, satisfaction was 66.7% and relative satisfaction was 18.5%. In Group B, satisfaction was 50.0% and relative satisfaction was 25.0%. Satisfaction of patients with the place of death was 81.5% in Group A, and 35.7% in Group B. Many families wished to have the nurse visit 2 times a week, and an hour at each visit. The great mental burden on the families who provide home care for patients with terminal cancer was clear for the questionnaire. Arrangement for a support system for patients and families, through visiting nurse services, is necessary in our hospital.