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A thermodynamic study of the phase stability of the mixed rare-earth barium cuprates, RE 0.5 RE ′ 0.5 Ba 2 Cu 3 O 7− x (RE/RE ′ BCO, RE=Y, RE ′ =Er, Yb) and ‘YBCO+25 wt.% BaF 2 ’ was carried out over the temperature range 800–960 °C and pO 2 range 3.0×10 −4 to 2.1×10 −1 atm O 2 , using a coulometric titration technique. At temperatures, T , less than the peritectic temperature, T p , the phase stabilities of the mixed rare-earth compounds lie between the two single rare-earth parent systems. However, at T > T p the phase stabilities of the mixed rare-earth compounds depend on the solubilities of the rare-earths in the melt. The stability of ‘YBCO+BaF 2 ’ is reduced compared to pure YBCO and is very close to pure ErBa 2 Cu 3 O 7− x (ErBCO).

BACKGROUND: Response rates to chemotherapy in relapsed, platinum resistant epithelial ovarian cancer remain poor. We have explored the effectiveness of weekly cisplatin combined with prolonged oral etoposide in this patient group. PATIENTS AND METHODS: Forty-two women with relapsed, advanced ovarian cancer were treated with cisplatin 60 mg/m2 on days 1, 8, 15, 29, 36 and 43 and oral etoposide 50 mg given from day 1-14 and day 29-43. In those who were responding and tolerating treatment (n = 13) oral etoposide 50 mg was continued for two further cycles (days 1-21 repeated every 28 days). The interval since last platinum containing chemotherapy was > 6 months in 28 patients and < 6 months in 16 patients. RESULTS: Thirty-six patients were evaluable for response according to CA 125 criteria giving an overall response rate of 44%. The response rate in evaluable patients declined with increasing numbers of previous treatments: 57% with one prior treatment, 42% with two, 40% with three or more. The response rate in patients who had received platinum chemotherapy within six months prior to treatment was 46%. The only significant non-haematological toxicity was nausea and vomiting in 4 patients who experienced greater than grade 2 toxicity. The number of patients experiencing haematological toxicity more than grade 2 was as follows: haemoglobin 3, white blood count 12, platelets 6. Sixteen patients had dose delays and two had dose reductions. CONCLUSION: We conclude that this short but intensive regimen provides worthwhile response rates, even in those patients who would ordinarily be considered refractory to platinum, and has an acceptable toxicity profile.

An ultrasonic mist pyrolysis system has been used to deposit in situ thick films of YBa 2 Cu 3 O 7− x , on single crystal LaAlO 3 . Growth temperatures of ∼900°C have been utilised to spray nitrate precursors at rates varying between 0.7 and 1 μm min −1 . Epitaxial growth of biaxially aligned ( T c endpoint∼85 K and T c onset∼91 K, with J c s of >10 4 A cm −2 1 T, 77 K. The film microstructure is very dense and grain connectivity is good. The main objective of this research has been to obtain high T c values and to further investigate the limitations of this very scalable route for conductor fabrication by studying film properties in relation to nitrate concentration and growth rate.

The relationship between conductivity and structure has been investigated in a new CuF 2 substituted BIMEVOX, Bi 2 V 1− x Cu x O 5.5−5 x /2 F 2 x , 0.10 ≤ x ≤ 0.20 (BICUVOF). The system has been characterised by X-ray powder diffraction and ac impedance spectroscopy. BICUVOF samples, in the compositional range studied, all show the tetragonal γ-phase structure when quenched from high temperature, however, there is evidence in the conductivity data of phase transitions associated with ordering phenomena at various temperatures. A large drop in conductivity is observed on solid solution formation. These observations are consistent with a mixed anion effect analogous to the mixed ion effect seen in cation conducting systems.

The influence of high Mg2+ dopant levels in BIMGVOX, Bi2MgxV1−xO5.5−3x/2 (0.05≤x≤0.40) on structure and conductivity has been investigated using X-ray powder diffraction and a.c. impedance spectroscopy. Four, compositionally dependent, structural ranges are observed at room temperature, with emergence of a new orthorhombic phase at high dopant levels. Generally the Arrhenius plots of conductivity show two linear regions the limits of which are compositionally dependent. The results have been correlated to the stability ranges of various polymorphs within the system.

A chemiluminescence (CL) micro-total analytical system is described for the analysis of codeine. The reaction involves the reduction of tris(2,2′-bipyridyl)ruthenium (III), (Ru(bipy)33+) to tris(2,2′-bipyridyl)ruthenium (II), (Ru(bipy)32+) with the emission of light. Reagents were moved around an etched glass chip with 200 μm channel using electroosmotic flow (EOF). The reaction emission was enhanced by the addition of the non-ionic surfactant Triton X-45 to the system and this surfactant was also shown to modify the electroosmotic flow. A linear calibration was obtained for the system over three-orders of magnitude with a correlation coefficient of 0.9999 and the limit of detection at 95% confidence was 8.3 × 10−7 mol l−1.

The structure and electrical conductivity of the fast oxide ion conducting system BIZNVOX, Bi 2 Zn x V 1- O 5.5- (0.05≤x≤0.27), were investigated using X-ray powder diffraction and ac impedance spectroscopy. There is a compositional dependence of the conductivity behaviour as a function of temperature. This behaviour was correlated with the stabilisation of various polymorphs within the system. The x = 0.10 composition was found to have one of the highest low temperature conductivities (σ 300 = 4.09× 10 -3 S cm -1 ) for any BIMEVOX compound.

Background: There is a need to delineate how the best available serum marker for ovarian cancer, CA 125 should be used in monitoring the treatment of individual patients, and in clinical trials. Patients and methods: The situations where measurement of CA 125 could alter the management of individual patients during therapy and at relapse were critically analysed. Precise definitions for response according to CA 125 were first developed and tested on 989 patients receiving first line therapy and have since been tested on over 2000 patients in phase 2 trials. Precise definitions for progression were developed from 71 patients during and on 255 patients both during and after initial chemotherapy. Results: In individual patient management, progression on initial chemotherapy can be demonstrated by serial rise in CA 125 suggesting the need for a change in therapy. A confirmed doubling of CA 125 from the upper limit of ormal during follow up accurately predicts relapse. This endpoint needs prospective testing for use in clinical trials. Precise definitions of response based on a 50% or 75% fall in CA 125 levels accurately predicts whether a cytotoxic agent is active against ovarian cancer. Conclusion: Precise definitions of response based on CA 125 should be used in phase 2 trials of new cytotoxic drugs.

The defect structure of γ-Bi 2 V 0.9 Ni 0.1 O 5.35 (BINIVOX, x =0.10) quenched from high temperature has been refined using X-ray and neutron powder diffraction data. The defect structure shows that oxide ion vacancies are exclusive to the equatorial positions around the Ni/V atom. Consideration of site occupancies, inter-site contact distances, and geometrical constraints yields two likely coordination environments for V/Ni, i.e. distorted tetrahedral and distorted octahedral. The percentage of V/Ni sites that are distorted tetrahedra may be calculated as 68% with the remainder as distorted octahedra.

Summary Background Renal disease in people with insulin-dependent diabetes (IDDM) continues to pose a major health threat. Inhibitors of angiotensin-converting enzyme (ACE) slow the decline of renal function in advanced renal disease, but their effects at earlier stages are unclear, and the degree of albuminuria at which treatment should start is not known. Methods We carried out a randomised, double-blind, placebo-controlled trial of the ACE inhibitor lisinopril in 530 men and women with IDDM aged 20–59 years with normoalbuminuria or microalbuminuria. Patients were recruited from 18 European centres, and were not on medication for hypertension. Resting blood pressure at entry was at least 75 and no more than 90 mm hg diastolic, and no more than 155 mm hg systolic. Urinary albumin excretion rate (AER) was centrally assessed by means of two overnight urine collections at baseline, 6, 12, 18, and 24 months. Findings There were no differences in baseline characteristics by treatment group; mean AER was 8.0 μg/min in both groups; and prevalence of microalbuminuria was 13% and 17% in the placebo and lisinopril groups, respectively. On intention-to-treat analysis at 2 years, AER was 2.2 μg/min lower in the lisinopril than in the placebo group, a percentage difference of 18.8% (95% CI 2·0–32·7, p=0·03), adjusted for baseline AER and centre, absolute difference 2.2 μg/min. In people with normoalbuminuria, the treatment difference was 1·0 μg/min (12·7% [−2·9 to 26·0], p=0·1). In those with microalbuminuria, however, the treatment difference was 34.2 μg/min (49·7% [−14·5 to 77·9], p=0·1; for interaction, p=0·04). For patients who completed 24 months on the trial, the final treatment difference in AER was 38·5 μg/min in those with microalbuminuria at baseline (p=0·001), and 0·23 μg/min in those with normoalbuminuria at baseline (p=0·6). There was no treatment difference in hypoglycaemic events or in metabolic control as assessed by glycated haemoglobin. Interpretation Lisinopril slows the progression of renal disease in normotensive IDDM patients with little or no albuminuria, though greatest effect was in those with microalbuminuria (AER ≥20 μg/min). Our results show that lisinopril does not increase the risk of hypoglycaemic events in IDDM.

Summary Background Background: In a previous phase I–II trial we showed that maximum tolerable dose (MTD) of 5-fluorouracil (5-FU) a weekly 48-hour continuous infusion (CI) was 3.5 g/m2. In a subsequent confirniative phase II trial with 85 evaluable patients, a 38.5% response rate was obtained, and a median survival of 12 months. These data were comparable to those achieved by biochemical modulation of 5-FU with leucovorin. On this basis we attempted to modulate high-dose 5-FU (3 g/m2) with oral leucovorin (LV) but the regimen too toxic and the dose had to be reduced. A new phase II trial with 2 g/m2/week plus oral leucovorin was planned. Patients and methods From July 1992 to June 1994, 110 previously untreated patients with advanced, measurable colorectal cancer were included in a multicenter study. The patients received, on an outpatient basis, 5-FU 2 g/m2 by continuous infusion for 48 hours once a week until progression or the appearance of toxic effects. Oral leucovorin (60 mg every six hours) was also given during the 5-FU infusion. Results Patients received a median dose intensity of 5-FU of 1.6 g/m2/week (range 0.9–2). Three complete responses and 36 partial responses were observed. The overall response rate was 37.5% (95% CI, 28% to 46.8%), the median time to progression 7.4 months and median survival 14.5 months. W.H.O. grade 3 diarrhea occurred in 27 patients (24.5%); grade 3 mucositis was observed in 9 (8.1%) patients and grade 4 in one. Grade 3 nausea and vomiting was reported in 13 (11.7%) patients, while grade 3 hand-foot syndrome was detected in only 5 (4.5%). Grade 4 leukopenia occurred in one patient and grade 3–4 thrombocytopenia in two. Conclusion Oral leucovorin modulation of weekly 48-hour continuous infusion of 5-FU at 2 g/m2 is an active regimen, with diarrhea and mucositis as the main limiting toxic effects. Its antitumor activity does not seem superior to that obtained with a weekly 48-hour continuous infusion of 5-FU alone at a dose of 3.5 g/m2.

The relationship of structure and conductivity has been investigated in the Co substituted BIMEVOX system Bi 2 V 1 − x Co x O 5.5 − 3x 2 , 0.07 ≤ x ≤ 0.25 (BICOVOX). This system has been characterised using a.c. impedance spectroscopy, X-ray and neutron diffraction. The Arrhenius plots all show two straight line segments, one at low temperatures, below 450 °C, and one at high temperatures, above 550 °C. In the intermediate region, 3 types of behaviour are observed which appears to be composition dependent. All compositions showed differences in conductivity after the first heating cycle. However, this thermal hysteresis persisted in subsequent heating-cooling cycles only in compositions below x = 0.10. All BICOVOX samples in the composition range studied show essentially the tetragonal γ-phase structure, with evidence for a superstructure modulation at low temperatures from the neutron data.

Summary Background: Many studies have shown that CA 125 levels frequently rise prior to clinical evidence of progression of ovarian cancer. For clinical trials an accepted definition of progression according to CA 125 is required. We therefore determined what change in CA 125 level was the most accurate predictor of relapse in patients on follow up after therapy for ovarian cancer. Patients and methods: Serial CA 125 levels were studied from 255 patients entering the North Thames Ovary Trial of 5 versus 8 courses of chemotherapy. An initial analysis was made 2 months after closure of the trial, a more detailed analysis was made after 81 confirmed relapses among evaluable patients and a final analysis was made one year later with longer follow-up. Results: On the basis of the results from the interim analyses and the cut-off level of 22-35 U/ml used by different laboratories, 30 U/ml was chosen as the upper limit of normal. In the final analysis a doubling of CA 125 from the upper limit of normal was defined as progression. Using this method sensitivity was 85.9%, specificity 91.3%, positive predictive value 94.8%, and negative predictive value was 77.8%. Insisting on a confirmatory elevated CA 125 level reduced the false positive rate to

The value of serial CA-125 measurements for predicting progression of ovarian carcinoma during therapy was calculated in 71 patients. The optimal algorithm that defined disease progression by CA-125 levels was either two values above 100 U/ml which had decreased by less than 50% over a minimum of 56 days, or a rise of 25% between successive samples plus a confirmatory sample. Of 13 patients with progressive disease according to the CA-125 criteria, 12 developed clinical evidence of progression within 12 months; predictions were false positive in 1, true negative in 50 and false negative in 8. Retrospective analysis showed that therapy and investigations costing 7979 pounds could have been avoided, if CA-125 assays costing 5470 pounds had been acted upon. The efficacy of the CA-125 algorithm is being independently verified to confirm that monthly CA-125 measurements whilst on treatment combine cost-effectiveness with a decrease in unpleasant interventions.

Identification and isolation of the specific antigen of M. tuberculosis with the aid of an antiserum against the antigen antibody complex prepared by Goudie's method from the serum of tuberculous patients is described. The position of the specific antigen on the disc electrophoresis column comprising four protein bands has been identified and separated. The antibody has been identified as IGg. More sophisticated techniques should enable the isolation of the specific antigen in practical amounts. The availability of such an antigen should greatly advance the serological diagnosis of tuberculosis.

1. 1. A comparative study has been made of some of the physico-chemical characteristics of vertebrate and invertebrate serum proteins. 2. 2. Proteins of electrophoretic mobility comparable to the immunoglobulins of human serum were shown to be present in all the vertebrate sera studied. Similar proteins were also found in many of the invertebrate sera. 3. 3. Analysis of sera on Sephadex G-200 showed that proteins with a sedimentation coefficient of approximately 19S were present in all the sera examined; proteins of other molecular sizes were found to show a greater variation in their distribution. 4. 4. Proteins which separated on the bases of molecular size were shown to be electrophoretically heterogenous. 5. 5. The significance of the presence of proteins with a sedimentation coefficient of approximately 19S in all the sera examined is discussed.

The combination of recombinant human interferon alpha A 9 MU daily intramuscularly and etretinate 50 mg daily orally was given to 25 patients with progressive advanced, metastatic melanoma. The treatment was well tolerated. Partial responses were seen in three (12%) patients lasting from 2 to 8 months. A further partial response was seen in one of three patients when they were given vindesine and DTIC whilst they continued receiving interferon and etretinate.

A combined cytochemical and biochemical study of the glycolytic enzyme activity in erythroblasts and erythrocytes in chronic renal failure has failed to show a diminished enzyme content compared with the erythroid cells in healthy matched controls. The results show that a glycolytic enzyme inhibitor recently reported in uraemic serum does not significantly depress enzyme activity in erythroid cells in vivo and is therefore unlikely to be the primary cause of the haematological defect in bone-marrow or peripheral blood-cells in chronic renal failure.