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Purpose: In order to prevent acute asthma attacks, an evaluation of QOL should also be required when diagnosing aggravating factors of asthma. In this study, we tried to clarify the [...]

PURPOSE: There is an unmet clinical need for palliative treatments with low toxicity for patients with recurrent advanced non-small cell lung cancer (NSCLC), as the current prognosis for this patient [...]

A DC corona discharge reactor was applied to remove sulfur dioxide (SO2) and benzene (C6H6) from N2-O2-H2O mixed gas in the temperature range from room temperature to 400 °C. When SO2 was removed, the temperature elevation caused the decrease of the removal efficiency of SO2. On the other hand, the removal efficiency of C6H6 was not significantly influenced by the temperature elevation. In the simultaneous removal of SO2 and C6H6 in the relatively low temperature range below 200 °C, the removal efficiency of SO2 is significantly inhibited by coexisting C6H6. When the simultaneous removal was conducted in the high temperature range, the removal efficiency of SO2 was not sensitive against the coexisting C6H6. On the other hand, the removal efficiency of C6H6 was almost independent of coexisting SO2 at all temperatures. A hypothesis of reaction mechanism was discussed based on radical reactions with SO2 and C6H6 to explain the trend observed in the experiment.

Cyclic ADP-carbocyclic-ribose (cADPcR, 2) is a biologically and chemically stable equivalent of cyclic ADP-ribose (cADPR, 1), a Ca²⁺-mobilizing second messenger. In this study, a series of 8-substituted analogues of cADPcR, namely the 8-chloro analogue 6 (8-Cl-cADPcR), the 8-azido analogue 7 (8-N3-cADPcR), the 8-amino analogue 8 (8-NH2-cADPcR), and the 8-phenylthio analogue 9 (8-SPh-cADPcR), were designed as effective pharmacological tools for studies on cADPR-modulated Ca²⁺ signaling pathways. These target compounds were synthesized by a convergent route via 8-Cl-cADPcR bisacetonide (14) as the common intermediate, in which a method for forming the intramolecular pyrophosphate linkage by activation of the phenylthiophosphate type substrate 15 with AgNO3 to produce 14 was used as the key step. The carbocyclic analogues were tested for activity in the sea urchin egg homogenate system. Compounds were assessed for their calcium-mobilizing effects and their ability to cross-desensitize with calcium release induced by a normally maximal concentration of cADPR, as well as cADPR antagonism of cADPR-evoked calcium release. While cADPcR was 3−4 times more potent than cADPR, the 8-substituted analogues were less efficacious, with 8-SPh-cADPcR largely acting as a competitive antagonist. Most surprisingly, given that 8-N3-cADPR and 8-NH2-cADPR are known as potent antagonists, 8-N3-cADPcR and 8-NH2-cADPcR were full agonists, but ca. 80 and 2 times less potent than cADPR, respectively. These data contribute to developing structure−activity relationships for the interaction of cADPR with its receptor.

Abstract: Background. SmithKline Beecham synthesized camptothecin analogs and identified nogitecan hydrochloride (topotecan) with a broad spectrum of antitumor activity and less toxicity than camptothecin. Because preclinical and overseas clinical data indicated the antitumor effect of nogitecan hydrochloride with a 5-day repeat-dose schedule, we carried out phase I studies in Japan to determine the maximum tolerated dose (MTD), pharmacokinetics, and antitumor effect of nogitecan hydrochloride. Methods. Phase I studies of nogitecan hydrochloride given by single and 5-day repeat dosing were carried out in patients with various solid tumors at 15 medical institutions in Japan. Pharmacokinetic evaluations were performed for both single and 5-day repeated dosing. Results. The dose-limiting factor (DLF) was reversible leucopenia, and the maximum tolerated dose (MTD) was higher than 22.5 mg/m2 in the single-dose study. In the 5-day repeat-dose study, the DLF was also reversible leucopenia, and the MTD was estimated to be 1.5 mg/m2 per day. The plasma concentration of nogitecan hydrochloride increased with increasing dose, and the half-life after single dosing ranged from 3 to 5 h. There was no evidence of accumulation or delayed excretion during 5-day repeat dosing. Conclusion. Based on these results and the finding that there were responders among patients treated at 1.5 mg/m2 per day by 5-day repeat dosing in overseas studies, 5-day repeat dosing of 1.2 mg/m2 per day, one dose level lower than the MTD, was selected for phase II studies in Japan.

The influence of a once-a-day sustained-release theophylline (Uniphyl®) on lymphocytes and eosinophils in the peripheral blood and sputum of patients with bronchial asthma was investigated. The peripheral blood lymphocytes included CD4, CD8, CD25 and HLA-DR. The sputum lymphocytes and eosinophils included CD4, CD8, CD25 and HLA-DR, and EG2, respectively. The results revealed that theophylline administration did not affect the numbers of activated CD4 and CD8 T lymphocytes in peripheral blood. No significant change in the lymphocyte count was observed in sputum, but the eosinophil count in the sputum decreased significantly after theophylline administration. EG2-positive eosinophils also decreased in number. CD4+HLA-DR+and CD4+CD25+T lymphocytes were significantly decreased, whereas CD8+T lymphocytes in the sputum were not significantly reduced in number. Respiratory function test showed that forced expiratory volume in 1 s was significantly increased after theophylline administration. The results suggest that a new once-a-day sustained-release theophylline formulation would be useful in the treatment of chronic respiratory tract inflammation.

Abstract: Background. We studied the clinical effect of recombinant human erythropoietin (r-huEPO) on anemia induced by two courses of cisplatin-based chemotherapy in patients with non-small cell lung cancer (NSCLC). Methods. Seventy-two patients with NSCLC were randomized into three groups, receiving 100, or 200 IU/kg of r-huEPO, or placebo. The r-huEPO and placebo were administered subcutaneously three times a week for 6 weeks, starting 2 weeks after the initiation of chemotherapy. Results. In the 53 evaluable patients, hemoglobin (Hb) levels at the nadir after the second cycle of chemotherapy were significantly elevated compared with the nadir after the first cycle in both r-huEPO treated groups, while this level was decreased in the placebo group. Hb levels at the end of the second course of chemotherapy (week 8) in both r-huEPO groups were higher than that in the placebo groups. No adverse drug reaction attributable to r-huEPO was observed. Serum erythropoietin levels after the administration of r-huEPO were higher than those after placebo administration. Conclusions. r-huEPO had an effect in preventing anemia in patients with NSCLC who had cisplatin-based chemotherapy.

Abstract: Background. The efficacy and safety of S-1, a new oral fluoropyrimidine, were evaluated in patients with non-small-cell lung cancer (NSCLC). The objective of this study was to determine whether the drug should be investigated in a late phase II study. Methods. Each treatment course consisted of an oral dose of S-1, 50 mg/body or 75 mg/body, twice a day for 28 days, followed by a 2-week washout period. Results. Fifty-six eligible patients were enrolled. Five of the 40 previously untreated patients (12.5%; 90% confidence interval, 6.2%–23.5%) showed a partial response (PR), and no tumor response was observed in the 16 previously treated patients. The median survival duration in all eligible patients was 8.4 months, with a 1-year survival rate of 27.3%. The incidences of grade 3 or more severe adverse effects were: anemia, 5.4%; leukopenia, 5.4%; neutropenia, 5.4%; thrombocytopenia, 1.8%; anorexia, 3.6%; diarrhea, 3.6%; and general fatigue, 5.4%. These effects disappeared after cessation of the drug or appropriate treatment. One patient died as a result of aggravated interstitial pneumonitis, but the relationship of this event to S-1 was not clear. Conclusion. S-1 showed modest activity with mild toxicity in the treatment of non-small-cell lung cancer. Based on this result, we will progress to the next stage of a late phase II study for advanced NSCLC, and a phase II study of S-1 and cisplatin for advanced gastric cancer. Final results will be reported as they are obtained.

The effect of a new thromboxane A2receptor antagonist, AA-2414, (±)-7-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)-7-phenylheptanoic acid, on dual broncho-constriction and airway hyper-reactivity in actively sensitized guinea-pigs was investigated. Immediate and late bronchial responses were seen 1–10 min and 4–7 h, respectively, after inhalation of antigen. In guinea-pigs pretreated with AA-2414, 5 mg/kg orally, the immediate bronchial response was inhibited. An administration of AA-2414 inhibited the late bronchial response. The numbers of eosinophils, neutrophils and macrophages, but not of lymphocytes, in bronchoalveolar lavage fluid were increased at 4 h after antigen inhalation. AA-2414 did not affect the numbers of total cells, eosinophils, neutrophils or macrophages. Sensitized guinea-pigs showed a significant airway hyper-reactivity to inhaled histamine, which was not influenced by an administration of AA-2414. Luminol-dependent chemiluminescence of airway-infiltrated cells from sensitized guinea-pigs stimulated with A23187 was slightly inhibited by AA-2414. These results show that AA-2414 inhibits the late asthmatic response and the production of oxygen radicals from airway-infiltrated cells

To find the angiographic lesions specific characteristics appropriate for intracranial percutaneous transluminal cerebral angioplasty (PTCBA).Forty-two clinically symptomatic patients with 42 haemodynamically significant intracranial lesions (% diameter stenosis >70) were treated by PTCBA between January 1992 and May 1996. Before the angioplasty treatment, the patients were classified into three groups according to the angiographic lesions' characteristics summarised as follows: type A, a short and concentric stenosis; type B, a tubular lesion, or an extreme eccentric lesion; and type C, a diffuse lesion. They were followed after PTCBA from one month to six years to compare between the three groups. Primary end points were death, stroke, or bypass surgery.The clinical success rates in type A, B and C groups were 92%, 86% and 33% (p=0.0032), respectively. Cumulative risks of fatal or nonfatal ischaemic stroke / ipsilateral bypass surgery in type A, B and C groups were 8%, 26% and 87% (p<0.0001), respectively. The cumulative risk of 8% in type A group patients appeared to be smaller than in historical studies.PTCBA for intracranial simple (type A) lesions produces a favourable clinical outcome for symptomatic patients.

These studies provide the first evidence for leptin as a novel placenta-derived hormone in humans, and suggests the physiologic and pathophysiologic significance of leptin in normal pregnancy and in pregnancies complicated with preeclampsia or gestational trophoblastic diseases. To elucidate the role of leptin in human pregnancy, further investigations on the following points are required.o1.Mechanism of resistance to high plasma leptin levels during pregnancy has not been elucidated. Studies on down-regulation of leptin receptor and changes in the plasma concentrations of leptin binding protein, which is identical to soluble leptin receptor, Ob-Re, may provide an answer to this question. 2.Possible candidates of the biological significance of placenta-derived leptin in pregnancy may be; a) effects on maternal glucose and lipid metabolism, b) regulation of placental function, and c) effects on fetal growth and development. 3.Identification of distribution of leptin receptors in intra-uterine tissues is crucial to understand the role of placenta-derived leptin during pregnancy.

The objective of this study was to assess the effect of ovine follicular fluid (FF) treatment (with or without FSH replacement) during the late follicular phase on plasma concentrations of gonadotrophins and the development of the ovulatory follicle. Ovarian steroid secretion and expression of mRNA encoding inhibin α and βA′ βBsubunits, P450 aromatase and P450 17α-hydroxylase were used as endpoints. After induction of luteolysis by injection of 100 μg cloprostenol on days 10–12, Scottish Blackface ewes were allocated to one of three groups: (1) control (n=7): no further treatment; (2) FF (n= 9): subcutaneous injections of 3 ml steroid-free ovine follicular fluid at 9 h intervals, 18 and 27 h after cloprostenol injection; (3) FF + FSH (n= 8): injections of follicular fluid as above plus subcutaneous injections of 0.36 iu ovine FSH at 6 h intervals, 18, 24, and 30 h after cloprostenol injection. Jugular venous blood samples were obtained via indwelling cannulae at 6 h intervals from 0 to 36 h after cloprostenol injection, and at 10 min intervals from 12 to 18 h (control phase) and from 30 to 36 h after cloprostenol injection (treatment phase). At laparotomy, 36 h after cloprostenol injection, ovarian venous blood was collected and ovaries were removed and processed for in situhybridization. Plasma concentrations of FSH, luteinizing hormone (LH) and oestradiol were determined by radioimmunoassay. Follicular fluid treatment resulted in a decrease (P< 0.001) in FSH concentrations associated with an acute decrease in ovarian steroid secretion (P< 0.01) and a specific depression in P450 aromatase, (P< 0.001), inhibin–activin βBsubunit (P< 0.05) and thecal LH receptor (P< 0.001) expression. Follicular fluid treatment had no effect on inhibin–activin α and βA′ subunit or P450 17α-hydroxylase expression. FSH co-treatment with follicular fluid restored circulating FSH concentrations to normal values and reversed some of the effects of follicular fluid (androstenedione, testosterone and progesterone secretion, and inhibin βBand thecal LH receptor expression) but not oestradiol secretion or P450 aromatase expression. It was concluded that the actions of follicular fluid are mediated via both central effects on pituitary FSH secretion and by direct ovarian effects on granulosa cell aromatase activity. The results indicate that follicular fluid contains a factor that inhibits aromatase activity of granulosa cells directly and may play a role in the selection of the dominant follicle.

In the metamorphosed manganese oxide ores of India, braunite is ubiquitous in all assemblages from chlorite to sillimanite grades. Chemical analyses of braunite from different prograde assemblages confirm the presence of a fixed R2+ (=Mn2++Mg+Ca) SiO3 molecule in the mineral. Element partitioning between coexisting braunite and bixbyite indicates a near-ideal mixing of Fe+3/ -Mn+3 in the phases. This also indicates that braunite became relatively ferrian while equilibrating with associated phases such as bixbyite, hollandite and jacobsite during prograde reactions. Petrogenetic studies show that as a general trend, prograde lower oxide phases appeared by deoxidation of higher oxide phases. But braunite, a more reduced phase than bixbyite, appeared early from deoxidation of pyrolusite in presence of quartz. Bixbyite could appear later from the reacting pyrolusite-braunite-quartz assemblage. Inferred mineral reaction paths and the general trend of pro-grade deoxidation reactions suggest that the composition of ambient fluid phase was internally buffered during metamorphism.

Abstract: This paper aims to ascertain the degree of equilibrium attained with respect to oxygen during metamorphism of non-carbonatic manganiferous sediments and the nature of mobility of oxygen in rocks of adjacent beds by measuring the composition of coexisting phases. Through algebraic analysis of the relevant phase equilibria, a difference of ≃17 kcal in $$u_{{\text{O}}_{\text{2}} } $$ in rocks of adjacent beds is obtained. This confirms the immobile nature of oxygen during metamorphism of manganiferous sediments.

The purpose of this study was to assess the safety and efficacy of percutaneous transluminal cerebral balloon angioplasty (PTCBA) of extra- and intra-cranial arteries by investigating procedural outcome. Eighty haemodynamically significant extra- and intra-cranial lesions (% diameter stenosis >70) in 74 clinically symptomatic patients were treated by elective and initial PTCBA between March 1991 and February 1996 and followed thereafter.Death, stroke including transient ischemia, surgery, or repeated angioplasty of restenosis or new lesions were regarded as cerebral events after the initial PTCBA. Crescendo ischaemic symptoms disappeared completely after clinically successful dilatation. The clinical success rate was 81% (65/80). Angiographic restenosis rate at 3 months was 22% (14/65).By life-table method, the death/stroke risk was 16% and death/stroke/surgery/repeated PTCBA risk was 49 % at 2 years following PTCBA, respectively.In conclusion, PTCBA successfully, decreased recurrent neurological symptoms and produced a favourable short-term outcome, whereas restenosis limited long-term benefit.

A phase I trial of the combination of irinotecan (CPT-11) with cisplatin in advanced non-small cell lung cancer (NSCLC) showed a very promising response rate of 54% in previously untreated NSCLC patients. This study was conducted to confirm the activity and toxicities of CPT-11 and cisplatin combination for previously untreated NSCLC in a multi-institutional phase II study. Seventy patients with stage IIIB or IV NSCLC received CPT-11 60 mg m(-2) intravenously (i.v.) on days 1, 8 and 15, and cisplatin 80 mg m(-2) (i.v.) on day 1 every 4 weeks. Assessments were made of response, survival and toxicities. Sixty-nine were eligible, and evaluable for toxicities and survival, and 64 patients evaluable for response. Thirty-three patients (52%; 95% confidence interval 39-64%) achieved an objective response, with one complete response (2%) and 32 partial responses (50%). The median duration of response was 19 weeks and the overall median survival time was 44 weeks. The 1-year survival rate was 33%. The major toxic effects were leucopenia and diarrhoea. Grade 3 or 4 leucopenia, neutropenia, and diarrhoea occurred in 32 patients (46%), 53 patients (80%), and 13 patients (19%) respectively. A combination of CPT-11 and cisplatin is very effective against non-small-cell lung cancer with acceptable toxicities.

Mn silicate-carbonate rocks at Parseoni occur as conformable lenses within metapelites and calc-silicate rocks of the Precambrian Sausar Group, India. The host rocks are estimated to have been metamorphosed at uppermost P-T conditions of 500–550°C and 3–4 kbar. The Mn-rich rocks contain appreciable Fe, reflected in the occurrence of magnetite(1) (MnO 1%), magnetite(2) (MnO 15%) and magnetite(3) (MnO 10%). Two contrasting associations of pyroxmangite, with and without tephroite, developed in the Mn silicate-carbonate rocks under isothermal-isobaric conditions. The former assemblage formed in relatively Fe-rich bulk compositions and equilibrated with a metamorphic fluid having a low XCO2 (<0.2), and the latter equilibrated with a CO2-rich fluid. Rhodochrosite+magnetite(1)+quartz protoliths produced the observed mineral assemblages on metamorphism. Partitioning of major elements between coexisting phases is somewhat variable. Fe shows preference for tephroite over pyroxmangite at the ambient physical conditions of metamorphism. Oxygen fugacity during metamorphism was monitored at or near the QFM buffer in tephroite bearing domains, and the fluid composition was buffered by mineral reactions in respective domains. As compared to other metamorphosed Mn deposits of the Sausar Group, the Mn silicate-carbonate rocks at Parseoni were, therefore, metamorphosed at much lower fO2 through complex mineral-fluid interactions.

Purpose: Foot venous pressure measurement is considered to be useful for assessing lower limb venous insufficiency, because venous hypertension is the main factor predisposing to venous insufficiency. In this study, we investigated the utility of foot venous pressure measurement in the evaluation of venous insufficiency. Methods: A total of 148 limbs of 101 patients with venous insufficiency associated with varicose veins and treated over 5 years were studied. The measurements assessed were percentage decrease in foot venous pressure with manual calf compression (%drop), rate of increase in foot venous pressure during a 4-second period after release of compression (4SR%), and time to 50% recovery of foot venous pressure (RT50). Results: A higher incidence of skin changes (clinical, etiologic, anatomic, and pathophysiologic classification classes 4 to 6) caused by venous insufficiency was associated with %drop, 4SR%, and RT50 values. Skin changes were found in more than 50% of the limbs with a %drop less than 50%, 4SR% more than 50%, or RT50 less than 4 seconds. After tourniquets were applied to occlude the superficial veins, limbs with severe below-knee deep venous reflux (%drop 60.3 +/- 14.6, 4SR% 36.7 +/- 30.2, RT50 13.9 +/- 14.7) showed significantly worse values than those with no reflux (%drop 79.9 +/- 3.2, 4SR% 8.1 +/- 3.1, RT50 48.9 +/- 17.9) or with mild above-knee reflux (%drop 77.0 +/- 5.0, 4SR% 7.1 +/- 3.2, RT50 46.9 +/- 26.7). After sclerotherapy or surgical treatment, including deep venous reconstruction for severe below-knee reflux, all limbs showed significant improvement in clinical manifestations and foot venous pressure values (%drop 68.1 +/- 7.5 to 76.5 +/- 5.8, 4SR% 33.1 +/- 12.9 to 12.7 +/- 7.6, RT50 7.5 +/- 4.2 to 20.1 +/- 6.5). Conclusion: Foot venous pressure measurements showed a good correlation with clinical severity and degree of venous reflux and were very useful for evaluating the outcome of therapy for venous insufficiency. (J Vasc Surg 1998;27:671-76.)

The accuracy of a new device for indirect blood pressure measurement was evaluated by comparison with the intra-arterial pressure measurement. The device is based on the Korotkoff's method using a cuff and a microphone, but is characterized by a two-channel recorder to monitor the cuff pressure and the events picked up by the microphone. The blood pressure is determined automatically by a computer program which analyzes the microphone signal during a cuff deflation, and manually by the same criteria to confirm the result. The comparison was carried out on 29 subjects undergoing catheterization of the brachial artery for clinical examination.

Abstract: In an attempt to determine the P/V relation in human limb veins noninvasively and to assess its accuracy, simultaneous measurements of electrical admittance, water displacement plethysmography, venous occlusive cuff pressure and intravenous pressure were carried out in 36 healthy subjects (29 males and 7 females; aged 20–46). The cuff pressure was controlled with a cuff inflator. There was a close and linear correlation between these two plethysmograms and between the direct intravenous and cuff pressure. These results suggest that the P/V relationship in human limb veins can be determined noninvasively by the measurement of electrical admittance change caused by the venous occlusive cuff pressure change controlled by the inflator.

Abstract: Static and dynamic (beat-to-beat) arterial viscoelastic properties were measured noninvasively in human fingers and forearms. The volume change and pressure change were detected simultaneously by admittance plethysmography and by sphygmomanometry using the vascular unloading technique in the index and middle finger, or vice versa. These simultaneous measurements were also made on the forearms of one side and the fingers of the other side. The arterial viscoelastic properties in these segments could be successfully determined at different transmural pressure levels from 0 mm Hg to around the mean arterial pressure.

We developed a mouse monoclonal antibody, S2n8, by immunizing mice i.p. with human decidual cells collected in the first trimester of pregnancy. By indirect immunofluorescence staining of frozen sections, S2n8 was found to react with decidual cells and endometrial stromal cells throughout the menstrual cycle, but not with endometrial glandular cells or with the endometrial surface epithelium. Judging from the fluorescence intensity, the antigen expression on stromal cells was weak in the proliferative phase, and became stronger in the secretory phase. Decidual cells in the first trimester of pregnancy and decidual cells at term showed strong expression of this antigen. Indirect immunofluorescence staining of enzymatically dispersed decidual tissue revealed that the S2n8 antigen was expressed on the decidual cell surface. Flow cytometric analysis of 12 freshly prepared stromal cell-enriched cell suspensions showed that 74.8-94.2% (mean +/- SD 86.1 +/- 6.6%) of the cells carried the antigen. The expression of S2n8 antigen on cultured stromal cells was enhanced by the addition of oestradiol and/or progesterone. The antigenic molecule was purified by immunoaffinity chromatography from decidua collected in the first trimester of pregnancy, and the molecular weight was estimated to be approximately 140 kDa. These findings indicate that the S2n8 antigen is a useful cell surface marker for stromal cells/decidual cells and is associated with their differentiation.

We have reported that the cytokines, interleukin-1 (IL-1), tumour necrosis factor alpha (TNF alpha), and interferon (IFN) alpha, beta, and gamma modulate the steroidogenic function of human luteinized granulosa cells in culture. In the present study we examined the interactions between these cytokines in modulating progesterone and oestradiol production by these cells. Neither IL-1 nor TNF alpha had significant effects on human chorionic gonadotrophin (HCG)-stimulated progesterone production, whereas IFN gamma (1-10 ng/ml) significantly reduced HCG-stimulated progesterone production by 26-37%. Concomitant treatment with IL-1 (1 ng/ml) did not further enhance the inhibitory effect of IFN gamma on HCG-stimulated progesterone production. In contrast, the combination of TNF alpha (1 ng/ml) and IFN gamma (10 ng/ml) acted synergistically to markedly inhibit HCG-stimulated progesterone production by 81%. In addition, IL-1 and TNF alpha, neither of which was effective alone, acted synergistically to reduce significantly HCG-stimulated progesterone production by 30%. The combination of TNF alpha and IFN gamma also markedly inhibited follicle stimulating hormone (FSH)-stimulated oestradiol production by 97%, a significantly greater inhibition than that obtained with either cytokine alone. These results suggest that the cytokines may interact to modulate the steroidogenic function of luteal cells in the developing corpus luteum.

A randomized trial of combination therapy with bestatin (30mg daily, every day) was performed in 238 patients with inoperable primary lung cancer from August, 1981 through April, 1984. Of the 238 patients, 227 were evaluable: 113 treated by bestatin combination therapy and 114 controls. There was no statistically significant difference in response rate or survival between the 2 groups. In squamous cell cancer response was observed in 34.5% of the bestatin group and 17.9% of the control group. The analysis, including Cox's proportional hazard model, revealed that the survival tended to be longer in the bestatin group (median survival 40 weeks) than in the control group (median survival 24 weeks; p = 0.051). This suggests that addition of bestatin might be beneficial in squamous cell cancer of the lung but further, more rigidly controlled, clinical trials are necessary before more definitive conclusions can be drawn.

Abstract.: The purpose of this study was to assess the safety and efficacy of percutaneous transluminal cerebral balloon angioplasty (PTCBA) of extra- and intra-cranial arteries by investigating procedural outcome. Eighty haemodynamically significant extra- and intra-cranial lesions (% diameter stenosis > 70) in 74 clinically symptomatic patients were treated by elective and initial PTCBA between March 1991 and February 1996 and thereafter followed. Death, stroke, surgery, or repeated angioplasty of restenosis or new lesions were regarded as cerebral events after the initial PTCBA. The procedural and clinical success rates were 81 % (65 of 80) and 81 % (60 of 74), respectively. Progressively ischaemic symptoms disappeared completely after clinically successful dilatation. Angiographic restenosis rate at 3 months was 22 %(14 of 65). By life-table method, the death/stroke risk was 16 %, and any cerebral event risk was 49 % at 2 years following PTCBA, respectively. The most common of first cerebral events presented was repeated angioplasty of restenosis. In conclusion, PTCBA has great efficacy in decreasing recurrent neurological symptoms and produces a favourable short-term outcome, whereas restenosis limits long-term benefit.

Summary Intracranial lipomas are very rare, probably congenital lesions. Though they can occur anywhere in the intracranial space, a good proportion of cases tend to be located around the midline. Review of the literature as well as our own three cases — which forms the basis of this article — shows that they are mostly asymptomatic. When symptoms occur, they are frequently the result of coexisting general clinical conditions. Lipomas used to be reported mainly as incidental findings at autopsy. Advances in neuro-imaging techniques have vastly improved the likelihood of their being discovered during life. At present however, significant increase in the reported incidence of these tumours is yet to be seen. Surgical extirpation of the tumour is not considered necessary in the majority of patients, many of whom show remarkable clinical improvement following shunt procedures for obstructive hydrocephalus as well as treatment of coexisting conditions such as epilepsy.

A new formulation of garnet-biotite Fe-Mg exchange thermometer has been developed through statistical regression of the reversed experimental data of Ferry and Spear. Input parameters include available thermo-chemical data for quaternary Fe-Mg-Ca-Mn garnet solid solution and for excess free energy terms, associated with mixing of Al and Ti, in octahedral sites, in biotite solid solution. The regression indicates that Fe-Mg mixing in biotite approximates a symmetrical regular solution model showing positive deviation from ideality withWFeMgbi=1073±490 cal/mol. ?Hrand ?Srfor the garnet-biotite exchange equilibrium were derived to be 4301 cal and 1.85 cal respectively. The resultant thermometer gives consistent results for rocks with a much wider compositional range than can be accommodated by earlier formulations.

Abstract: The purposes of this study were to determine the optimal time for initial follow-up angiography, the restenosis rate after successful intracranial percutaneous transluminal cerebral angioplasty (PTCBA), and finally to identify lesion-specific characteristics for predicting successful angioplasty. Thirty-five patients underwent PTCBA with follow-up angiography 3 and 12 months later. Although 27 lesions were adequately dilated, permanent complications occurred in 3 patients. The restenosis rate at 3 months was 29.6 %; patients without restenosis at 3 months remained free from vessel narrowing at 12 months. Restenosis occurred on severe, eccentric lesions, total occlusions or extremely angulated lesions. There was a strong correlation between sufficient dilatation and lower re- stenosis rate, and concentric and short lesions (type A). We conclude that the optimal time for initial angiographic follow-up is 3 months after PTCBA. PTCBA is most suitable for type A lesions with higher success, lower morbidity and lower restenosis rates.

AbstractMg-Mn amphibole (tirodite), with or without pyroxmangite in the total absence of pyroxenes and high-calcic pyroxenoids, occurs in the Mn silicate rocks of the Sausar Group, India. The rocks were metamorphosed to amphibolite facies condition (T~ 650°C, P~ 6 kbar). Tirodite-pyroxmangite pairs developed in both carbonate-free and rhodochrosite-bearing assemblages. Also tirodite coexists with either kutnahorite or manganoan calcite in the absence of pyroxmangite. Mineral reactions inferred from modal abundances and compositions of the phases indicate stabilization of the amphibole alone from a bivalent cation-bearing residual unbuffered XCO2system with XMn< 0.3. On the other hand, tirodite-pyroxmangite pairs appeared in unbuffered low to intermediate XCO2assemblages with XMn> 0.35. Pyroxenes and high-calcic pyroxenoids did not appear in the present situation, though they occur elsewhere in rocks with broadly similar contents of immobile components. Closely associated assemblages of diverse mineralogy suggest that the XMnand XCO2, rather than the physical conditions of metamorphism, are the decisive factors in promoting the observed phase assemblages.

AbstractManganiferous garnets occur in metamorphosed Mn silicate-oxide and silicate-carbonate-oxide rocks of the Sausar Group, India. The garnets of the carbonatic rock show maximum calderite content (~50 mole%). Increased Ca content in the bulk has been observed to be sympathetically related to the concentration of calderite, rather than the expected andradite component of the garnets. This is the consequence of the preferential partitioning of Ca in coexisting pyroxmangite and/or carbonate. Petrochemical characteristics of the diverse assemblages in response to the physical conditions of metamorphism show that the calderite solubility in manganiferous garnet is not only a function of pressure. Such characteristics only indicate that the mobile components in the bulk influenced the mineralogy of the assemblages at the ambient physical conditions of metamorphism, and this in turn controlled the calderite solubility in garnet.

ABSTRACTA suite of garnet‐wollastonite‐scapolite‐bearing calcsilicate granulites from the Eastern Ghats has been investigated to document the controls of mineral reactions during the metamorphic evolution of the deep continental crust. The rocks studied show heterogeneity in modal mineralogy and phase compositions in millimetre‐sized domains. Textural relations, and the compositional plots of the phases, established that the clinopyroxene exerts a strong influence on the formation and composition of garnet in the complex natural system. P‐Testimates using the vapour‐independent equilibria involving garnet define a near isobaric cooling path from c.850C at c.5.5–5.2 kbar. The deduced trajectory tallies well with the terminal segment of the overall retrograde P‐Tpath construed from the associated rocks using well‐calibrated thermobarometers. The ubiquitous occurrence of wollastonite and scapolite in the main calcsilicate body suggests low aCO2during peak metamorphic condition. Fluid compositions constrained from mineral‐fluid equilibria of the garnet‐bearing assemblages show domainal variations as a function of the compositions of the solid phases, e.g. garnet and clinopyroxene. A quantitative log/CO2‐log/O2diagram has been constructed to depict the stability of the different calcsilicate assemblages as functions of the compositions and the behaviour of these fugitive species. The results of the mineral‐fluid equilibria and the quantitative fluid/rock ratio calculations, in conjunction with the topological constraints, imply vapour‐deficient meta‐morphism in the rocks studied. It is argued that fO2during peak metamorphism was monitored by the ambient fO2. Subsequently, during retrogression, different domains evolved independently, whereas the fluid composition was controlled by the mineral‐fluid equilibria.

A phase II trial was conducted to evaluate the efficacy and toxicity of the Egorin's carboplatin dosing formula with 14-day oral etoposide in 38 elderly patients with small-cell lung cancer (SCLC). The overall response rate was 81%. Median survival times were 15.1 months for 16 limited-disease (LD) and 8.6 months for 22 extensive-disease (ED) patients. Myelosuppression was the principal side-effect. This regimen is an active regimen in the treatment of elderly SCLC patients.

Sixty-three patients with extensive-stage small-cell lung cancer were randomized to receive either cyclophosphamide, vincristine, doxorubicin and etoposide (CODE) alone or CODE plus recombinant human granulocyte colony-stimulating factor (rhG-CSF). rhG-CSF administration in support of CODE chemotherapy resulted in increased mean total received dose intensity for all drugs (P = 0.03) with a significant improvement in survival (P = 0.004).

Soluble cytokeratin fragment 19 levels were measured with an enzyme immunoassay method developed by Boehringer Mannheim (Enzymun-Test CYFRA 21-1) in the serum of 185 patients with lung cancer [149 with non-small-cell lung cancer (NSCLC) and 36 with small-cell lung cancer (SCLC)] and 97 patients with benign lung diseases in order to determine its clinical usefulness in the diagnosis of lung cancer and follow-up of treatment. We used the cut-off value of 3.5 ng ml-1, established by the Japan CYFRA research group. This cut-off value is based on calculations using the receiver operating characteristic approach instead of using the 95% specificity approach recommended by other authors. The resulting sensitivity and specificity for the group of all lung cancer patients were 65.4% and 84.5% respectively. The sensitivity was highest (76.1%) for squamous cell carcinoma and lowest (44.4%) for SCLC. For NSCLC patients, when CYFRA 21-1 levels were analysed by node (N) factor, patients who presented with mediastinal lymph node metastasis (N2 or N3) demonstrated higher serum CYFRA 21-1 levels (5.6; interquartile range 3.2-11.5 ng ml-1) than patients without mediastinal node metastasis (N0 or N1, 3.9; interquartile range 2.2-10.0 ng ml-1; Mann-Whitney U-test, P = 0.0373). We compared the discriminatory power of CYFRA 21-1 with that of other tumour markers including carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and neuron-specific enolase (NSE). The area under the curve (AUC) of each ROC curve was calculated using the CLABROC program for statistical analysis. CYFRA 21-1 appeared to have the most discriminatory power of the markers tested in the diagnosis of lung cancer. In serial measurements of 14 patients receiving chemotherapy or radiotherapy, a high degree of correlation was noted between serum levels of CYFRA 21-1 and extent of clinical response (Wilcoxon, P = 0.0093).

We have conducted a Phase I trial to determine the maximum tolerated dose of CPT-11 together with a fixed dose of cisplatin in patients with advanced lung cancer, and the dose-limiting toxicities of this combination. Fourteen previously untreated patients with stage IIIB or IV disease were treated with CPT-11 (90-min intravenous infusion on days 1, 8, and 15) plus cisplatin (60 mg m-2, intravenously on day 1). The starting dose of CPT-11 was 60 mg m-2, and diarrhea was the dose-limiting toxicity at the 90 mg m-2 dose level. All three patients (all four cycles) given 90 mg m-2 of CPT-11 experienced grade 3 diarrhea. Hematologic toxicity was relatively mild. Elimination of CPT-11 was biphasic with a mean (+/- s.d.) beta half-life of 11.36 +/- 7.26 h. The mean terminal half-life of the major metabolite (7-ethyl-10-hydroxycamptothecin; SN-38) was 22.13 +/- 13.28 (s.d.) h, and modest escalation of the CPT-11 dose from 80 mg m-2 to 90 mg m-2 resulted in a statistically significant apparent increase in the plasma concentrations of SN-38. There were one complete response (7%) and five partial responses (36%) among the 14 patients for an overall response rate of 43%. The recommended dose for Phase II studies is 80 mg m-2 of CPT-11 and 60 mg m-2 of cisplatin.

We attempted to clarify whether serum levels of a carboxy-terminal fragment of ProGRP, ProGRP(31-98), could serve as a more accurate tumour marker in patients with SCLC than neuron-specific enolase (NSE). ProGRP(31-98) and NSE were measured retrospectively in 101 newly diagnosed untreated patients with SCLC, 111 with non-small-cell lung cancer (NSCLC) and 114 patients with non-malignant lung diseases. ProGRP(31-98) and NSE levels were determined using a sandwich enzyme-linked immunosorbent assay. Sensitivity in SCLC patients was 72.3% for ProGRP(31-98) and 62.4% for NSE. Comparing the area under curve (AUC) of 'receiver operator characteristics' of ProGRP(31-98) with that of NSE, ProGRP(31-98) was the more powerful marker in the diagnosis of SCLC (P = 0.0001). Serum levels of ProGRP(31-98) were higher in the 40 patients with extensive disease than in the 61 patients with limited disease (P = 0.0082). ProGRP(31-98) was significantly higher in patients with pure small-cell carcinoma than in patients with mixed small-cell/large-cell carcinoma (P = 0.02). In serial measurement in 16 patients responding to treatment, a high degree of correlation was noted between the decrease in serum ProGRP(31-98) levels and clinical response during the second week after treatment (P = 0.0045). These results indicate that the determination of serum ProGRP(31-98) levels plays an important role in the diagnosis and treatment of SCLC patients.

Abstract: Although it is controversial whether total occlusions of intracranial arteries can safely be opened by angioplasty, we treated six patients with total occlusions of the middle cerebral artery by percutaneous transluminal cerebral angioplasty (PTCBA) in the chronic stage after a stroke, on average 10 weeks. We successfully opened four total occlusions less than 3 months old, while two total occlusions more than 3 months old could not be opened. No complications occurred. Even in the chronic stage, PTCBA for total occlusion of intracranial arteries can be done safely.

Mafic granulites occurring as conformable lenses within khondalite, leptynite, and calc-silicate rocks from the Anantagiri-Araku areas of the Eastern Ghats belt contain orthopyroxene, clinopyroxene, garnet, quartz, ilmenite, and plagioclase as major constituents. Orthopyroxene contains (100) lamellae of clinopyroxene, and clinopyroxene contains (100) orthopyroxene lamellae and (001) spindles of pigeonite. Reaction textures indicate formation of garnet through coupling of two reactions, viz. orthopyroxene + anorthite = garnet + clinopyroxene + quartz and anorthite + ilmenite - $$hematite_{ss}$$+ quartz = garnet + ilmenite + $$O_{2}$$. Thermobarometry indicates exsolution of pigeonite at ~950°C, of (100) clinopyroxene in orthopyroxene and vice versa at 750-820°C and formation of garnet at around 700-725°C, 7 kb, all in response to cooling of the rock. This shows a nearly isobaric cooling path subsequent to peak metamorphic conditions. Subsequently, the rock suffered nearly isothermal decompression to 5 kb. Hydration and K-metasomatism of the assemblage occurred at lower temperatures (~500°C) in the final phases. The structural characteristics and thermal history of the mafic granulites suggest that the mafic rocks were emplaced during the culmination of prograde metamorphism accompanying a compressive orogeny. Mafic magmas could have contributed significantly to enhance the thermal budget for granulite facies metamorphism. This study, therefore, attests to the very high metamorphic temperatures (as high as 1000°C regionally) attained by the Eastern Ghats granulites.