Novel experimental setup for megahertz X-ray diffraction in a diamond anvil cell at the High Energy Density (HED) instrument of the European X-ray Free-Electron Laser (EuXFEL).

The high-precision X-ray diffraction setup for work with diamond anvil cells (DACs) in interaction chamber 2 (IC2) of the High Energy Density instrument of the European X-ray Free-Electron Laser is described. This includes beamline optics, sample positioning and detector systems located in the multipurpose vacuum chamber. Concepts for pump-probe X-ray diffraction experiments in the DAC are described and their implementation demonstrated during the First User Community Assisted Commissioning experiment. X-ray heating and diffraction of Bi under pressure, obtained using 20 fs X-ray pulses at 17.8 keV and 2.2 MHz repetition, is illustrated through splitting of diffraction peaks, and interpreted employing finite element modeling of the sample chamber in the DAC.

Ayrshire and Arran coronary prevention programme--baseline risk factor survey.

Scotland has very high mortality rates for coronary heart disease in both men and women. The Ayrshire and Arran health Board Area is co-terminus with four local government districts which all have male coronary mortality rates above the Scottish average. A survey of lifestyle and coronary risk factors was conducted in these four districts in preparation for the launch of a Prevention Programme's 'Healthy Heart Campaign'. This survey will be used as a baseline for evaluation of lifestyle modification and risk factor change over the next 5-10 years. The information provided by the survey is valuable to the direction and targeting of the Prevention Programme. The methods developed in this survey could be used for evaluation of other coronary prevention programmes. Similar data has been collected from another 20 districts as part of the Scottish Heart Health Study and has been distributed to all the Scottish mainland health boards.

Endemic Kaposi's sarcoma: incidence and risk factors in the West Nile District of Uganda.

Out of 72 Kaposi's sarcoma patients diagnosed between 1951 and March 1976 at Kuluva Hospital, West Nile District, Uganda, 64 with known co-ordinates were plotted on a map. Sixty-two of these were noted to live at an altitude of 853 metres or more (greater than or equal to 2,800 feet). Twenty-four patients were thought to be still alive and visits were made to their homes. Space-time grouping of four cases was noted on two occasions, although analysis did not reveal statistically significant clustering. A case-control study employing an interview questionnaire with 32 variables was performed on 19 patients and their age- and sex-matched neighbourhood controls, and sera were collected from both groups and from their families for estimation of viral antibody titres. The results demonstrated that cases tended to be post-pubertal males, a high proportion of whom had been bitten by a blood-sucking insect identified as being similar to Haematopota. Both cases and controls had raised antibody levels to cytomegalovirus, but cases obtained their drinking water more commonly from rivers whereas controls tended to use water from springs, boreholes or pipes.

Electrical stimulation with Pt electrodes. VII. Dissolution of Pt electrodes during electrical stimulation of the cat cerebral cortex.

Procedures are described for determining trace quantities of Pt released into brain tissue directly beneath cortical surface stimulation electrodes. Implanted electrodes (1.1 mm Pt discs) were stimulated for 4.5 h, 9 h and 36 h (4 X 9 h/day) with balanced biphasic pulses (20 micro C/cm2 or 100 micro C/cm2 per phase, 50 Hz), following which tissue 0-2 mm beneath stimulation electrodes and the encapsulating tissue adherent to electrodes was excised and analyzed for Pt. A time-dependent increase in Pt concentration was observed between 4.5 h (4-20 ng Pt/stimulation site) and 9 h (50-339 ng Pt/site) of stimulation at 100 micro C/cm2 with nearly all of the Pt located in the encapsulating tissue associated with the electrodes. Somewhat less Pt was observed in the 36 h samples, and it was almost equally distributed between the encapsulating tissue of the electrodes and the first millimeter depth of underlying brain tissue. Little or no Pt was found at electrode sites receiving 20 micro C/cm2 pulses. Control brain tissue samples as well as samples of blood, CSF and kidney were negative for Pt. The findings indicate that the rate of Pt dissolution gradually decreases during in vivo stimulation, and that dissolved Pt may slowly move away from stimulation sites, possibly by diffusion or fluid exchange.

Preparation of etched tantalum semimicro capacitor stimulation electrodes.

The ideal electrode for stimulation of the nervous system is one that will inject charge by purely capacitive processes. One approach is to exploit the type of metal-oxide combination used in electrolytic capacitors, e.g., Ta/Ta2O5. For this purpose, fine tantalum wire (0.25 mm diam) was etched electrolytically at constant current in a methanol solution of NH4Br containing 1.5 wt % H2O. Electrolytic etching produced a conical tip with a length of ca. 0.5 mm and shaft diameters ranging from 0.10 to 0.16 mm. The etched electrodes were anodized to 10 V (vs. SCE) in 0.1 vol % H3PO4. The capacitance values normalized to geometric area of etched electrodes ranged from 0.13 to 0.33 micro F mm-2. Comparison of these values to the capacitance of "smooth" tantalum anodized to 10 V (0.011 micro F mm-2) indicated that the degree of surface enhancement, or etch ratio, was 12-30. The surface roughness was confirmed by scanning electron microscopy studies which revealed an intricate array of irregularly shaped surface projections about 1-2 micrometers wide. The etched electrodes were capable of delivering 0.06-0.1 micro C of charge with 0.1 ms pulses at a pulse repetition rate of 400 Hz when operated at 50% of the anodization voltage. This quantity of charge corresponded to volumetric charge densities of 20-30 micro C mm-3 and area charge densities of 0.55-0.88 micro C mm-2. Charge storage was proportionately higher at higher fractional values of the formation voltage. Leakage currents at 5 V were ca. 2 nA. Neither long-term passive storage (1500 h) nor extended pulsing time (18 h) had a deleterious effect on electrode performance. The trend in electrical stimulation work is toward smaller electrodes. The procedures developed in this study should be particularly well-suited to the fabrication of even smaller electrodes because of the favorable electrical and geometric characteristics of the etched surface.

Electrical stimulation with Pt electrodes. V. The effect of protein on Pt dissolution.

The effect of protein on the charge-induced dissolution of Pt stimulation electrodes was studied in an in vitro system. Biphasic pulses (+/- 400 mA, +/- 400 microC cm-2 geom.) were applied to smooth Pt bead electrodes (surface area = 0.03-0.08 cm2) in a buffered saline solution containing 0.075-0.2 mg/ml human serum albumin; pulse solutions were analysed periodically for dissolved Pt by flameless atomic absorption spectrometry. The incorporation of protein in the pulse solution drastically altered the dissolution behaviour of Pt electrodes. Whereas dissolution in organic saline solutions proceeded essentially in a linear fashion, the rate in protein solution decreased with time and asymptotically approached zero. The passage of electric charge was required for the observed inhibition to develop but was not required to maintain it. In contrast, the constant presence of at least 0.15 mg/ml protein in the pulse solution was required for inhibition to develop and continue. Higher concentrations of protein did not enhance the observed inhibition. These findings bear favourably on the prospect for in vivo use of Pt stimulation electrodes: the dissolution process now appears to place no greater restriction on the acceptable pulse parameters than do other irreversible reactions such as H2O electrolysis.

Electrical stimulation with pt electrodes. IV. Factors influencing Pt dissolution in inorganic saline.

Trace analysis has shown that Pt electrodes can suffer appreciable dissolution when used to apply biphasic current pulses of the type used in neural stimulation. The dissolution occurs even under conditions where other irreversible faradaic reactions, e.g., H2O electrolysis, are avoided. In the present study, factors influencing the dissolution of Pt electrodes during biphasic pulsing in neutral inorganic saline have been examined. The findings are consistent with the behaviour of Pt electrodes reported in other inorganic media. In a given test, the quantity of Pt dissolved was found to be a linear function of the aggregate anodic or cathodic charge injected. Therefore, dissolution 'rates' can be conveniently expressed in terms of nanograms of Pt per coulomb injected, e.g., 100 ng C-1. Most of the Pt went into solution as Pt (II) species, so the above rate would correspond approximately to 100 p.p.m. of the anodic charge per pulse. For anodic-first (AF) pulses, charge density was the major factor controlling dissolution, whereas for cathodic-first (CF) pulses, pulse duration had the greater influence. Depending on the polarity (AF or CF), charge density, and duration of the biphasic pulse, the dissolution rate for smooth bead electrodes ranged from 30 to 300 ng C-1. Lower rates were achieved with platinized electrodes but in the absence of organic solutes, it is unlikely that Pt dissolution can be completely suppressed.

Changes in motochondrial calcium metabolism after treating mastocytoma cells with N6,O2'-dibutyryladenosine 3',5' cyclic monophosphate.

Comparison of Ca2+ uptake by isolated mouse liver mitochondria, and mitochondria prepared from mastocytoma cells grown with and without N6,O2'-dibutyryladenosine 3',5' cyclic monophosphate (DB cyclic AMP) and theophylline showed several differences in their capacity to take up and retain calcium. In particular mitochondria from DB cyclic AMP-treated mastocytoma cells took up more Ca2+ than mitochondria from untreated mastocytoma cells. Ca2+ uptake by mitochondria from DB cyclic AMP-treated cells was also increased in the presence of oxalate whereas oxalate did not affect Ca2+ uptake by mitochondria from untreated mastocytoma cells and it reduced Ca2+ uptake by mouse liver mitochrondria. The results suggest that inhibiting the growth of mastocytoma cells with DB cyclic AMP alters their mitochondrial Ca2+ metabolism.

Antibody patterns to herpesviruses in Kaposi's sarcoma. II. Serological association of American Kaposi's sarcoma with cytomegalovirus.

The prominent finding of this extended serologic analysis on American and African Kaposi's sarcoma (KS) patients and appropriately matched control groups is the detection of a specific serologic association of cytomegalovirus (CMV) with American KS patients. All American KS sera contained CMV antibodies and their geometric mean titers (GMT) were significantly higher than those in sera of melanoma patients (GMT ratio k = 5.3 to 7.7 by complement fixation [CF], k = 8.9 by indirect hemagglutination [IHA]) or in sera of age- and sex-matched healthy controls (k = 12.6 to 16.0 by CF, k = 12.6 by IHA). The result is strongly reminiscent of the data obtained previously for European KS. Although the GMT to CMV of African KS patients were similar to the GMT of the American KS groups, their significance cannot be demonstrated due to the high background of CMV infections in the control groups. Complex mechanisms are hypothesized, by analogy with the Epstein-Barr virus (EBV) involvement in Burkitt's lymphoma (BL), for a CMV involvement in the development of KS.

Electrical stimulation with Pt electrodes: Trace analysis for dissolved platinum and other dissolved electrochemical products.

A conservative requirement for 'safe' electrical stimulation is the absence of chemical changes adjacent to the stimulating electrodes. In electrochemical terms, this means that charge transfer processes producing dissolved species must be avoided. With this restriction, the aim of this study has been to establish the maximum charge density that can be passed during each half of a biphasic stimulation pulse. Possible dissolved species resulting from faradaic reactions at the Pt/saline interface include chloride oxidation products (ClO-, ClO3-, etc.) H+ or OH- ions and Pt ions. For balanced biphasic pulses, neither Cl- oxidation nor pH shifts appear likely to constitute significant problems and the most difficult problem to avoid appears to be metal dissolution. Pt dissolution has been monitored by UV spectrophotometric analysis and, because protein interferes with the analysis, the tests were run in inorganic saline solution. Results are presented in the form of nomographs which relate Pt dissolution to the charge density per pulse and the current density. Specific recommendations for minimizing Pt dissolution include the use of platinized electrodes, the restriction of charge densities per pulse to greater than or equal to 300 muC/geom cm2 of electrode surface, and preferably the use of cathodic-first biphasic pulses.

Twice weekly prophylactic therapy in haemophilia A.

Factor VIII-containing materials were administered to four severely affected haemophiliacs twice weekly in doses calculated to raise the factor VIII level to either 15% or 30% of average normal. The pooled results from those patients with statistically similar baseline bleeding frequencies showed a significant reduction in bleeding frequency on both doses in the first 48 hours. The 30% dose produced a more significant reduction than the 15% dose in the first 24 hours, but there was no significant difference between the two doses in the second 24 hours. It appears that to reduce the bleeding frequency of severely affected haemophiliacs by 60% would require a two-and-a-half-fold increase in therapeutic materials. A 90% reduction would need nine times the amount of material currently in use.

Active specific immunotherapy for ovarian cancer.

Ten patients with advanced or recurrent ovarian cancer were treated with a combination of chemotherapy and active specific immunotherapy after tumour stasis had been induced. They were inoculated with irradiated allogeneic cryopreserved tumour cells and B.C.G. once monthly in addition to receiving conventional chemotherapy. The overall duration of "remission", median survival, and projected 24-month actuarial survival in the patients receiving immunotherapy were apparently better than in a retrospectively matched control group treated by chemotherapy alone.

Improvement in lacrimal and salivary secretions after alkali therapy in Sjøgren's syndrome with renal tubular acidosis.

A patient with Sjøgren's syndrome developed renal tubular acidosis which led to systemic acidosis and potassium depletion. Treatment with Shohl's solution and potassium supplements was followed by subjective improvement in tear flow, salivary flow, and by disappearance of bronchitic symptoms. Detailed objective assessments were then made during the next year, twice on treatment and twice without. These confirmed the subjective impression of improvement.

Tumour associated immunity and immunocompetence in ovarian cancer.

Cell-free extracts of autologous ovarian cancer cells evoked a delayed hypersensitivity response (DHR) in skin in four out of six patients in remission from disease and none of seven patients in relapse. These initial results appear to be consistent with in vitro blastogenic assay using the same autologous extracts. To assess whether diminished tumour-associated immunity was due to impaired cell-mediated immunocompetence, blastogenic responses to purified protein derivative of tuberculin (PPD), a secondary recall antigen, and phytohaemagglutinin (PHA) were assessed. Impaired responses to PHA were seen in the relapse group of patients, but responses to PPD did not appear to be impaired in this group.

Tumour-associated immune responses and isolated carcinoembryonic antigen and alpha feto-protein levels related to survival in ovarian cancer patients.

The presence of a tumour-associated immune response in 37 patients with ovarian cancer as assessed by blastogenesis (lymphocyte transformation) evoked by ovarian cancer cell extracts, has been correlated with survival following the test. The difference in these responses is unlikely to be accounted for on the basis of general impairment of cell-mediated immuno-competence. Serum carcinoembryonic antigen (CEA) was also determined in 27 ovarian cancer patients to assess its prognostic significance. Raised CEA levels and absence of blastogenic response to tumour cell extract during relapse are associated with a worse prognosis but neither of these parameters are significant in remission. Possible applications of these findings to the clinical management of ovarian cancer patients are discussed. Serum alpha feto-protein levels measured by radioimmunoassay were not found to be raised in any of the 32 ovarian cancer patients in whom it was measured.

Tumour antigenicity in ovarian cancer.

The blastogenic response to a crude cell extract of ovarian cancer cells has been studied in 48 patients with ovarian cancer (9, autologous, 39 allogeneic), in 26 female controls matched for age and in 18 female patients with other types of cancer in remission from disease. The responses in ovarian cancer patients in remission and relapse were considered separately. The blastogenic responses to cell extracts of foetal ovary, foetal lung, foetal liver and normal adult ovary were also assessed in a proportion of all 3 groups. The blastogenic responses to ovarian cancer and foetal ovary cell extracts were found to be significantly greater in the ovarian cancer patients in remission than in the controls, but the responses to ovarian cancer extract were not greater in the relapse group or in patients with other cancers. As a blastogenic response to normal ovarian extract was also present in some of these patients, the data so far do not support the hypothesis of a tumour specific antigen. This tumour associated response may be occurring to determinants in foetal or adult ovarian tissue to which the patient becomes sensitized in malignant disease. The response is complex and the nature of the antigen requires further analysis.