Dealing with Community Mental Health post the Fukushima disaster: lessons learnt for the COVID-19 pandemic.

Under the COVID-19 pandemic, mitigation of psychological distress is required. At present, the demand for remote intervention for the numerous affected people is increasing, and telephonic support can be useful. Since the Fukushima nuclear disaster in 2011, we have been developing a large-scale telephonic support system and implementing brief interventions for the Fukushima people identified at risk of psychological problems such as depression and post-traumatic stress disorder. In this article, we report the lessons from the Fukushima disaster that can be applied to the COVID-19 pandemic and describe how the telephonic intervention facilitates easier access to psychological help for people with a broad range of psychological distress who are not able to visit treatment or care resources. In our telephonic intervention, we first sent a mental health and lifestyle survey to the people affected by the Fukushima disaster. The counselor team then provided telephonic intervention to high-risk persons as identified on the basis of the survey results. The individuals had expected to receive from the telephonic system help mainly in the form of stress-coping methods, social resource information such as schools, public offices or medical facilities, and lifestyle advice. Since we also experienced that psychological care for telephone counselors was necessary to mitigate the substantial emotional burden, we used the following three approaches: (i) regular supervision of the telephone counseling methods, (ii) seminars for improvement of counseling skills and (iii) individual psychological support. The positive loops between counselors and consulters will help advance a society affected by a disaster.

Blockage by adenovirus E4orf6 of transcriptional activation by the p53 tumor suppressor.

The adenovirus E4orf6 protein is shown here to interact with the cellular tumor suppressor protein p53 and to block p53-mediated transcriptional activation. The adenovirus protein inhibited the ability of p53 to bind to human TAFII31, a component of transcription factor IID (TFIID). Earlier work demonstrated that the interaction of p53 with TAFII31 involves a sequence near the NH2-terminus of p53, whereas the E4orf6-p53 interaction occurs within amino acids 318 to 360 of p53. Thus, the E4orf6 protein interacts at a site on p53 distinct from the domain that binds to TAFII31 but nevertheless inhibits the p53-TAFII31 interaction.

Two domains of p53 interact with the TATA-binding protein, and the adenovirus 13S E1A protein disrupts the association, relieving p53-mediated transcriptional repression.

The tumor suppressor gene product p53 can activate and repress transcription. Both transcriptional activation and repression are thought to involve the direct interaction of p53 with the basal transcriptional machinery. Previous work has demonstrated an in vitro interaction between p53 and the TATA-binding protein that requires amino acids 20 to 57 of p53 and amino acids 220 to 271 of the TATA-binding protein. The present results show that a 75-amino-acid segment from the carboxy terminus of p53 also can bind to the TATA-binding protein in vitro, and this interaction requires amino acids 217 to 268 of the TATA-binding protein, essentially the same domain that is required for interaction with the amino-terminal domain of p53. A carboxy-terminal segment of p53 can mediate repression when bound to DNA as a GAL4-p53 fusion protein. The amino- and carboxy-terminal p53 interactions occur within the domain on the TATA-binding protein to which the adenovirus 13S E1A oncoprotein has previously been shown to bind. The 13S E1A oncoprotein can dissociate the complex formed between the carboxy-terminal domain of p53 and the TATA-binding protein and relieve p53-mediated transcriptional repression. These results demonstrate that two independent domains of p53 can potentially interact with the TATA-binding protein, and they define a mechanism--relief of repression--by which the 13S E1A oncoprotein can activate transcription through the TATA motif.

Modulation of hormonal induction of tyrosine aminotransferase and glucocorticoid receptors by aflatoxin B1 and sterigmatocystin in Reuber hepatoma cells.

Employing Reuber rat hepatoma cells, H4-II-E, the effects of aflatoxin B1 (AFB1) and sterigmatocystin (STC), which exhibit a similar cytotoxicity but a marked difference in hepatocarcinogenicity, on the hormonal induction of tyrosine aminotransferase (TAT), on glucocorticoid receptors, and on their nuclear acceptor sites were investigated. AFB1 strongly inhibited hydrocortisone-inducible TAT activity. The IC50 value was 0.2 micrograms/ml. AFB1 also showed weak inhibitory effects on insulin- and dibutyryl cyclic AMP-inducible TAT activities. In contrast, the IC50 of STC on hydrocortisone-inducible TAT activity was 3.5 micrograms/ml, about 10 times higher than that of AFB1. Dibutyryl cyclic AMP- and insulin-inductions were not depressed by STC. AFB1 inhibited the formation of cytosolic glucocorticoid receptor-hormone complexes (GRCs) but STC did not. Moreover, AFB1, activated in vitro by the microsomal cytochrome P-450 system, interfered more markedly in the formation of cytosolic GRCs than STC did. Sucrose density gradient analysis of GRCs and Scatchard analysis revealed that AFB1 and STC mainly impaired glucocorticoid receptors and GRC-acceptor sites, respectively. The present data suggest a marked difference between AFB1 and STC with regard to the inhibition of hormonal induction of liver specific enzymes.

Indomethacin-induced radiosensitization and inhibition of ionizing radiation-induced NF-kappaB activation in HeLa cells occur via a mechanism involving p38 MAP kinase.

Although ionizing radiation (IR) activates multiple cellular factors that vary depending on dose and tissue specificity, the activation of NF-kappaB appears to be a well-conserved response in tumor cells exposed to IR. Recently, it also has been demonstrated that nonsteroidal anti-inflammatory agents inhibit tumor necrosis factor and interleukin-1-induced NF-kappaB activation and act as radiosensitizing agents. These observations reinforce the growing notion that NF-kappaB may be a protective cellular factor responding to the cytotoxicity of IR and other damaging stimuli. As such, we addressed the idea and mechanism that NF-kappaB is a downstream target of the nonsteroidal anti-inflammatory agent indomethacin and is involved in the process of radiosensitization. In this study, we report that indomethacin inhibited IR-induced activation of NF-kappaB and sensitized HeLa cells to IR-induced cytotoxicity at similar concentrations. Pretreatment of HeLa cells with SB 203580, a pyridinyl imidazole compound that specifically inhibits p38 mitogen-activated protein kinase (MAPK), abrogated the ability of indomethacin to inhibit IR-induced activation of NF-kappaB and diminished the indomethacin radiosensitizing effect. In addition, the transient genetic activation of p38(MAPK) inhibited IR induction of NF-kappaB gene expression in the absence of indomethacin. Finally, permanently transfected cell lines genetically unable to activate NF-kappaB, because of expression of a dominant negative I-kappaBalpha gene, demonstrated increased sensitivity to IR-induced cytotoxicity. Taken together, these results suggest that p38 MAPK is a target involved in indomethacin-induced radiosensitization and that NF-kappaB may be one downstream target in this process.

More complex transcriptional regulation and stress response by MOF.

MOF (males absent on the first) was initially discovered as a dosage compensation factor that regulates the epigenetic acetylation of histone H4 lysine 16. In this issue, Sheikh et al. demonstrate that MOF expression is not required for normal kidney tissue function but is required for maintaining transcriptional regulation under conditions of stress. This work along with results from previous investigators highlights the importance of the cell lineage-chromatin modification interaction in determining transcriptional programs and physiological outcomes under normal and stress conditions.

Interactions between adenovirus E1A and members of the AP-1 family of cellular transcription factors.

We have studied interactions between bacterially produced E1A linked to Sepharose and the various DNA-binding proteins present in HeLa cell nuclear extracts (NE). DNA-binding activities and cross-reactive polypeptides recognizing the cAMP-responsive element (CRE) and the activator protein 1 (AP1) sites were bound to the E1A column, whereas nuclear factor 1 (NF1) and the activator protein 2 (AP2) DNA-binding activities were not retained by E1A. The binding activities that were retained belonged to the CRE and JUN protein family, as judged by Western blot analysis. Authentic CRE-BP1, c-Jun and c-Fos proteins produced by in-vitro translation also bound to the E1A column. However, efficient binding of in-vitro-translated CRE-BP1 and c-Fos proteins to E1A required preincubation with NE. We show here that immobilized E1A sequesters several cellular upstream transcription activators, and suggest a role for members of the AP1 family of transcription factors in E1A-mediated gene regulation.

Pharmacokinetic study of S-1, a novel oral fluorouracil antitumor drug.

S-1 is a novel oral fluorouracil antitumor drug that combines three pharmacological agents: tegafur (FT), which is a prodrug of 5-fluorouracil (5-FU); 5-chloro-2,4-dihydroxypyridine (CDHP), which inhibits dihydropyrimidine dehydrogenase (DPD) activity; and potassium oxonate (Oxo), which reduces gastrointestinal toxicity. Phase I and early Phase II clinical trials have already been completed. On the basis of the results of these trials, 80 mg/m2/day, given daily in two divided doses after breakfast and supper, a 28-day consecutive oral regimen is recommended. In this study, we investigated the pharmacokinetics of 5-FU, intact FT, CDHP, and Oxo, after administration of S-1, at a standard dose of 80 mg/m2/day, in advanced cancer patients. Twelve patients were recruited to the study; 5 patients with gastric cancer, 4 with colorectal cancer, and 3 with breast cancer. Among them, analysis was conducted on 12 patients for single administration and on 10 patients for consecutive administration. The initial dose of S-1 for each patient was determined according to his/her body surface area (BSA) as follows: for BSA < 1.25 m2, 80 mg/body/day; for 1.25 m2 < or = BSA < 1.5 m2, 100 mg/day; and for 1.5 m2 < or = BSA, 120 mg/day. For single administration, half of the standard dose was used. For 28-day consecutive administration, the standard dose was given daily in two divided doses. The average single dose per BSA was 35.9 mg/m2 (31.7-39.7 mg/m2). Pharmacokinetic parameters of plasma 5-FU were as follows: Cmax, 128.5 +/- 41.5 ng/ml; Tmax, 3.5 +/- 1.7 h; AUC(0-14), 723.9 +/- 272.7 ng x h/ml; and T(1/2), 1.9 +/- 0.4 h. In the 28-day consecutive regimen, there were no fluctuations in pharmacokinetics nor any drug accumulation. Because the pharmacokinetics of orally administered S-1 is almost similar to that of continuous i.v. infusion of 5-FU, we concluded that S-1 may improve patients' quality of life.

Elevation of circulating plasma cytokines in cancer patients with high plasma parathyroid hormone-related protein levels.

Parathyroid hormone (PTH) and PTH-related protein/peptide (PTHrP) bind to the same PTH/PTHrP receptor and stimulate osteoblasts to secrete pro-inflammatory cytokines like interleukin (IL)-6. In patients with primary hyperparathyroidism, elevation of plasma levels of tumor necrosis factor (TNF)-alpha and IL-6 was also described. We, therefore, postulated that PTHrP secreted from cancer cells stimulates the secretion of cytokines and causes increases in their blood levels. Blood concentrations of several cytokines (TNF-alpha, IL-1beta, IL-5, IL-6, IL-8, IL-11 and IL-12) in cancer-bearing patients with or without elevation of blood PTHrP were measured by ELISA. The patients with high plasma PTHrP levels (n=29, intact PTHrP: 8.5 +/- 1.4 pmol/l, normal: <1.1) had higher serum type 1 collagen C-telopeptide (ICTP). Twenty of the patients were hypercalcemic. Plasma concentrations of TNF-alpha, IL-6 and IL-8 were significantly increased in patients with high PTHrP, in either the presence or absence of hypercalcemia. The concentrations of TNF-alpha and IL-6 were also significantly correlated with those of PTHrP. Our observations indicate that high plasma levels of PTHrP in cancer-bearing patients contribute not only to the development of hypercalcemia, but also to the development of the syndrome caused by an excess of pro-inflammatory cytokines.

Late phase II study of novel oral fluoropyrimidine anticancer drug S-1 (1 M tegafur-0.4 M gimestat-1 M otastat potassium) in advanced gastric cancer patients.

S-1 is a novel oral anticancer drug, composed of tegafur (FT), gimestat (CDHP) and otastat potassium (Oxo) in a molar ratio of 1:0.4:1, based on the biochemical modulation of 5-fluorouracil (5-FU). CDHP inhibits dihydropyrimidine dehydrogenase (DPD), an enzyme which degrades 5-FU, and maintains prolonged 5-FU concentrations in the blood and tumours. Oxo is distributed in the gastrointestinal tract at a high concentration after oral administration and alleviates gastrointestinal toxicity due to 5-FU. S-1 improves the tumour-selective toxicity of 5-FU by the actions of two modulators, CDHP and Oxo. We conducted a late phase II clinical trial of S-1 as an open trial in patients with advanced gastric cancer, to confirm its antitumour effect and adverse reactions. 51 patients with advanced gastric cancer were enrolled in the trial. S-1 was administered orally twice daily after meals, at a standard dose of 80 mg/m2/day. One course consisted of consecutive administration for 28 days and 14 days' rest. Administration was repeated over four courses. A complete response was obtained in 1 patient and partial responses in 24 patients, producing a response rate of 49% (25/51) (95% confidence interval (CI) 35.9-62.3%). The incidence of adverse reactions was 78% (40/51) and that of adverse reactions of grades 3 and 4 was 20%. Adverse reactions of grades 3 and 4 included a decrease in the haematocrit, leucopenia, granulocytopenia, diarrhoea, malaise and proteinuria. No serious unexpected adverse reactions were observed. In conclusion, S-1 was effective and well tolerated in patients with advanced gastric cancer.

Transforming region of 243R E1A contains two overlapping but distinct transactivation domains.

Conserved regions 1 and 2 as well as the amino terminus of E1A are required for the transforming activity of the E1A oncoprotein. We show here that the amino terminus of 243R E1A has transactivation activity when brought to a promoter in yeast. Recruitment to a specific promoter is essential. Mutagenesis studies correlated the transactivation function with the extreme amino terminus and the conserved region 1 of E1A. Cotransfection assays in rodent cells confirmed that two overlapping but distinguishable domains, amino acids 1-65 and 37-80, can transactivate independently when targeted to a promoter. We also observed that when recruited to the proliferating cell nuclear antigen (PCNA) promoter, the amino-terminal region was sufficient to transactivate the PCNA promoter. On the other hand, deletion of the amino terminus of E1A resulted in failure to induce PCNA expression. Fusion of VP16 with the amino-terminal-deleted E1A mutant was able to restore the ability to induce the PCNA promoter. We further show that the amino-terminal region also is required for 243R E1A to repress the transactivation mediated by a universal transactivator DBD.VP16 and DBD.E1A. This repression could be specifically relieved by overexpression of TBP but not TFIIB. In addition, we show that the amino terminus of E1A is involved in in vitro interaction with the TATA binding protein (TBP). Thus the amino-terminal transforming region of E1A may regulate cellular gene expression in species that are distant in evolution via a common mechanism, functionally targeting TBP.

Can esophagectomy cure cancer of the thoracic esophagus involving the major airways?

To evaluate the effects of aggressive operation for esophageal cancer invading the trachea and main bronchi, we investigated retrospectively 62 patients with proven tracheobronchial involvement who underwent thoracotomy for esophagectomy between 1973 and 1993. We operated unless the tumor was assessed to be definitely unresectable. Esophagectomy was possible in 55 patients, and the resectability rate was 95% after preoperative computed tomography and bronchoscopy became routine. After esophagectomy, no residual cancer lesion was recognizable macroscopically in 53% of patients. The hospital mortality rate in esophagectomy cases was 7% in the past 8 years. The outcome in patients who underwent curative resection was significantly favorable (p < 0.0001), and the 2-year survival was 51%. The patients with nonresectable cancer all died within 6 months compared with a 23% 1-year survival rate for palliative esophagectomy cases (p < 0.006). Among patients with tracheobronchial involvement assessed as resectable on computed tomography and bronchoscopy, a considerable proportion benefited from aggressive therapy with esophagectomy. The possibility of complete cure was high, especially when the cancer responded well to preoperative therapy and no lymph nodes were involved.

Epirubicin-containing high-dose chemotherapy followed by autologous hematopoietic progenitor cell transfusion for patients with chemotherapy-sensitive metastatic breast cancer: results of 5-year follow-up.

PURPOSE: Conventional chemotherapy for metastatic breast cancer results in very few long-term survivors. With a view to overcoming this problem, we hypothesized that a higher rate of complete response (CR) would lead to more long-term survivors. Therefore, we conducted a phase II study of epirubicin-containing high-dose chemotherapy (HDC) followed by autologous hematopoietic progenitor cell transfusion in patients who were sensitive to induction chemotherapy. METHODS: The induction chemotherapy consisted of doxorubicin 60 mg/m2, cyclophosphamide 750 mg/m2 and fluorouracil 750 mg/m2 on day 1. Supported by G-CSF, this chemotherapy was repeated for at least three cycles at intervals of 2 weeks until the achievement of > 50% tumor regression. The HDC comprised epirubicin 120 mg/m2 on day 1, cyclophosphamide 60 mg/kg on days 1 to 3 and thiotepa 6 mg/kg on days 1 to 3, followed by autologous bone marrow transplantation and peripheral blood stem cell transfusion. RESULTS: Of 25 patients who achieved a partial response to the induction chemotherapy, 17 were treated with the HDC. Of the 15 patients evaluable for response, 10 achieved a CR (67%), giving an overall CR rate of 43% (10/25). The disease-free survival rate at 5 years was 27%. The median duration of overall survival was 21 months and the overall survival rate at 5 years was 31%. However, the survival curves were not significantly different from those of the historical controls who achieved a CR or PR to conventional chemotherapy. There were three early deaths, one as a consequence of disease progression and two treatment-related (sepsis and heart failure). Diarrhea (grade 3, 76%) and stomatitis (grade 3-4, 29%) were the dose-limiting toxicities. CONCLUSIONS: The present study suggests that epirubicin-containing HDC is able to induce a high rate of CR, but its benefit in terms of survival is still unclear. To determine whether HDC can achieve a cure in some patients, further studies in a larger number of patients, with a longer follow-up, are necessary.

A randomized trial of adriamycin, cyclophosphamide, ftorafur (ACF) and adriamycin, cyclophosphamide, ftorafur, methotrexate (ACFM) in patients with advanced breast cancer.

A prospective randomized trial was conducted comparing the clinical response of 60 patients with advanced breast cancer to a combination of adriamycin, cyclophosphamide, and oral ftorafur (ACF), or to a combination of ACF plus methotrexate (ACFM). The response rate was 12 of 28 (43%) in ACF and 18 of 30 (60%) in ACFM. Responses were seen more frequently in patients in whom fewer than two organs were involved, and responses at dominant metastatic sites were equal for the two arms. The response duration was 21 + (3.5-49.5+) months with ACF, as against 6.9 (1.9-30.8+) months with ACFM (P less than 0.05). The median survival time from start of therapy was 20.8+ months for ACF, while that for ACFM was 13+ months (statistically not significant). The major toxicities were hair loss, GI toxicity, and leukopenia. The response rate with ACFM was higher than that with ACF, but the addition of methotrexate to ACF did not increase the complete response rate or prolong response duration.

An unusual association of monoclonal gammopathy, paroxysmal nocturnal haemoglobinuria and myelodysplastic syndrome transformed into acute myeloid leukaemia: coexistence of triple clonal disorders.

An unusual association of paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML) and monoclonal gammopathy is reported. A 60-year old male, who had a history of IgA monoclonal gammopathy, presented with haemoglobinuria and colic pain. Flow cytometry showed CD55negative/59dim peripheral red cells, and bone marrow examination disclosed MDS. Eleven months, he developed later AML with disappearance of the PNH clones, although the monoclonal gammopathy persisted. The relationship between PNH and MDS has not fully been assessed, although our findings indicate that these triple clonal disorders, all coexisted in one patient.

Detection and quantitation of thymidylate synthase mRNA in human colon adenocarcinoma cell line resistant to 5-fluorouracil by competitive PCR.

BACKGROUND: Thymldylate synthase (TS) is an important target of cancer chemotherapeutic agents, such as 5-fluorouracil (FU). To investigate mechanisms of resistance to FU, we tried to detect TS mRNA in the human colon adenocarcinoma cell lines. MATERIALS AND METHODS: SNU-C1 (C1) and its FU-resistant cell line, SNU-C1/FU (C1/FU) were used for this study. Total RNA was isolated by the AGPC method, then competitive PCR and northern blot were done to detect TS mRNA. RESULTS: Using sets of primers covering the 3'-untranslated region of TS mRNA, PCR products were amplified from cDNA prepared from both C1 and C1/FU in their logarithmic growth phases. However, only cDNA prepared from C1/FU was amplified in the stationary phase. The amount of mRNA was quantified by competitive PCR technique in both cell lines, using another set of primer to amplify the product in the stationary phase. The amount of TS mRNA in C1/FU was found to be four times more than that found in C1. In addition, TS catalytic activity of C1/FU was approximately 2-times higher than that of C1. Southern blot analysis revealed that no TS gene amplification or rearrangement in genomic DNA was detected in these cell lines. CONCLUSIONS: This PCR technique is applicable for detecting TS mRNA, and the TS mRNA level was found to be increased 1.5-fold (as detected by northern blot analysis) and 4-fold (measured by competitive PCR), leading to enhanced TS catalytic activity in C1/FU in contrast to its parent cell line, C1; thus accounting for one possible resistant mechanism to FU.

Indomethacin lowers the threshold thermal exposure for hyperthermic radiosensitization and heat-shock inhibition of ionizing radiation-induced activation of NF-kappaB.

PURPOSE: It is well established that salicylate and several other non-steroidal anti-inflammatory agents (NSAID), including indomethacin, can activate the heat-shock response, albeit at high concentrations. This is significant since heat shock significantly alters the cellular cytotoxic response to ionizing radiation (IR). It was previously shown that heat shock, as well as NSAIDs, inhibits IR-induced activation of NF-kappaB and that NF-kappaB protects against IR-induced cytotoxicity. Hence, it is hypothesized that pretreatment with indomethacin before heating will lower the temperature and heating times required to inhibit the activation of NF-kappaB and induce significant hyperthermic radiosensitization. MATERIALS AND METHODS: Experiments were performed in HeLa cell lines and the DNA-binding activity was determined by EMSA. Cellular radiosensitivity was determined by clonogenic assay. RESULTS: HeLa cells pretreated with indomethacin showed a decrease in the temperature-time combination necessary to inhibit IR-induction of NF-kappaB DNA binding. In addition, clonogenic cell survival assays using identical conditions showed an indomethacin dose-dependent enhancement of hyperthermic radiosensitization. Thus, similar concentrations of indomethacin both lowered the threshold thermal exposure to inhibit activation of NF-kappaB DNA-binding and increased the sensitivity of tumour cells to hyperthermic radiosensitization-induced cytotoxicity. In HeLa cells treated with N-alpha-tosylphenylalanyl-chloromethyl ketone (TPCK), a serine protease inhibitor that blocks activation of NF-kappaB, an increase in radiosensitivity was observed. Interestingly, no additional cell killing was observed when heat shock was added to cells treated with TPCK before IR, suggesting a possible common cytotoxic pathway. CONCLUSIONS: The results demonstrate that indomethacin lowers the temperature-time conbination necessary to induce several physiological processes associated with the heat-shock response. Furthermore, NSAID may be potential adjuvants in improving the clinical effectiveness of hyperthermia in radiation therapy.

Reliability of data obtained by radionuclide angiocardiography in follow-up studies with special reference to intra- and interobserver variations.

The reproducibility of the data obtained by radionuclide angiocardiography was studied in terms of the intra- and intervariations of three technicians. Three parameters were chosen: the left ventricular ejection fraction (LVEF), the 1/3 filling fraction (1/3FF), and the ratio of the time from end systole to the point of peak filling rate against the entire diastolic period (TRPFR). First, each technician studied an independent consecutive series of 40 patients for the initial analysis. The original data of each patient, composed of 26 frames for one beat, were stored on an optical disc for the intra- and intervariation studies. In this study, analysis of the volume curve was performed by using both 3rd order and 4th order Fourier series. The region of interest (ROI) for the left ventricle, which was set for the initial analysis, was recorded by Polaroid photography to be used as a reference for the later analyses for the variation studies. The least variation was noted in the LVEF not only for the intravariation study but also for the intervariation study, no matter which order of the Fourier series was used. However, the 3rd order Fourier series seemed to give better curve fitting to avoid fluctuation of the diastolic parameters. The results indicate that we can expect more steady and reliable information from LVEF than from the diastolic parameters, even when various technicians perform the follow-up study of a particular patient.

Comparison of detectability of visual field abnormality by frequency doubling technology in primary open-angle glaucoma and normal-tension glaucoma.

PURPOSE: To compare the effectiveness of frequency doubling technology (FDT) in detecting abnormalities in primary open-angle glaucoma (POAG) and in normal-tension glaucoma (NTG). METHODS: Twenty-nine POAG patients (29 eyes) and 27 NTG patients (27 eyes) were studied. All subjects underwent testing with program C-20 of FDT with appropriate corrective lenses. RESULTS: No significant differences were observed between the two groups in mean age, mean deviation (MD), and pattern standard deviation (PSD) measured by the Humphrey Field Analyzer (HFA). The correlation between MD values determined by HFA (x) and FDT (y) is represented by y = 0.60x - 2.7 (r = 0.78, P <.01) in the POAG group and y = 0.59x + 0.6 (r = 0.81, P <.001) in the NTG group. Although the average MD measured by FDT was significantly lower in the POAG group than in the NTG group (P <.05), no significant difference was found in average PSD between the two groups. In early glaucoma cases (MD > or = -5 dB by HFA), a larger proportion of cases in the POAG group than in the NTG group had lower significance level of MD determined by FDT than by HFA (P <.02). At many test points on the temporal periphery in the FDT, the mean sensitivity was lower in the POAG group than in the NTG group; whereas no significant differences among HFA test points were observed. CONCLUSIONS: Frequency doubling technology detected visual field abnormalities in POAG cases more sensitively than in NTG cases. This finding indicates that the pathogenesis of My-cell damage is rather different in POAG and NTG.

Comparative study of incadronate and elcatonin in patients with malignancy-associated hypercalcaemia.

The clinical usefulness of incadronate was compared with elcatonin in 26 patients with malignancy-associated hypercalcaemia. Data from 21 and 24 patients could be used to assess efficacy and safety, respectively. Eleven patients were given a single 10-mg intravenous infusion of incadronate and 10 received twice-daily intramuscular injections of 40 IU of elcatonin for 7 consecutive days. After treatment, corrected serum calcium levels decreased significantly in both groups. The anti-hypercalcaemic effect of elcatonin was characterized by its rapid onset, with serum calcium levels reduced 1 day after administration. In contrast, the anti-hypercalcaemic effect of incadronate was more sustained but only became apparent a few days after infusion. Evaluation of symptoms revealed significantly greater improvement rates in the incadronate group compared with the elcatonin group. Adverse drug reactions were observed in three patients in the incadronate group, i.e. mild and transient fever in two cases and exacerbation of disturbance of consciousness in one case. These findings suggest that incadronate produces more marked and sustained hypocalcaemic effects than elcatonin, and that co-administration of these two drugs may yield both rapid and sustained control of malignancy-associated hypercalcaemia.