Patient preferences for the delivery of bad news - the experience of a UK Cancer Centre.

The primary aim of this study was to assess how patients would prefer to be given their cancer diagnosis in a typical UK cancer centre. Two hundred and forty-four patients attending the oncology outpatient department at the Leicester Royal Infirmary, UK, were recruited. Patients were invited to complete the Measure of Patients' Preferences questionnaire, write comments on their own experience of the breaking bad news consultation and choose their preferred role in decision making. Over 90% of questionnaires were completed. Patients rated the items addressing the message content of the consultation as more important than the facilitative or the supportive aspects. Over 80% of patients wrote a detailed account of their experiences, of which 60% were satisfied with the consultation. Most of the patients who were dissatisfied commented on the unsympathetic or pessimistic manner of the doctor. The majority of patients wanted a collaborative role in decision making. Regarding the cancer diagnosis, the majority of patients have information needs, want to be involved in treatment decisions and know their prognosis. The difficulty for physicians is how to meet individual information needs, give hope, but not deliver unrealistic expectations.

Quantitation of silibinin, a putative cancer chemopreventive agent derived from milk thistle (Silybum marianum), in human plasma by high-performance liquid chromatography and identification of possible metabolites.

Silibinin has recently received attention as a potential cancer chemopreventive agent because of its antiproliferative and anticarcinogenic effects. A simple and specific reversed-phase high-performance liquid chromatography method was developed and validated for the quantitation of silibinin in human plasma. Sample preparation involved simple protein precipitation, and separation was achieved on a Waters Atlantis C18 column with flow rate of 1.0 mL/min at 40 degrees C and UV detection at 290 nm. Silibinin was detected as two peaks corresponding to trans-diastereoisomers. The peak area was linear over the investigated concentration range (0-5000 ng/mL). The limits of detection were 2 and 1 ng/mL for the two diastereoisomers (d1 and d2), with a recovery of 53-58%. This method was utilized to detect silibinin in plasma of colorectal patients after 7 days of treatment with silipide (silibinin formulated with phosphatidyl choline).

Use of DNA restriction fragment length polymorphisms to document marrow engraftment and mixed hematopoietic chimerism following bone marrow transplantation.

We have studied the feasibility of using DNA restriction fragment-length polymorphisms (RFLP) to study marrow engraftment in 27 patients after allogeneic bone marrow transplantation, and have compared these results with those obtained using red blood cell antigens, cytogenetics, and immunoglobulin allotypes. Using highly polymorphic DNA probes, we have documented stable chronic mixed hematopoietic chimerism, have identified transient mixed chimeras, have excluded mixed chimerism with high probability in retrospective studies even when a pretransplant DNA sample was not available, have documented marrow engraftment in the early posttransplant period, and have studied the origin of leukemic cells in patients with recurrent disease. We have evaluated the advantages and disadvantages of several genetic markers and have developed tentative statements concerning the prognosis of patients with mixed chimerism. We conclude that DNA RFLP are powerful and practical genetic markers in bone marrow transplantation studies and that further studies of mixed hematopoietic chimerism are warranted.

Influence of carbohydrate ingestion on immune changes after 2 h of intensive resistance training.

Thirty strength-trained subjects were randomized to carbohydrate (CHO) or placebo (Pla) groups and lifted weights for 2 h (10 exercises, 4 sets each, 10 repetitions, with 2- to 3-min rest intervals). Subjects received 10 ml x kg(-1) x h(-1) CHO (6%) or Pla beverages during the weight training bout. Blood, saliva, and vastus lateralis muscle biopsy samples were collected before and after exercise. Blood cell counts were determined, and plasma was analyzed for IL-6, IL-10, IL-1 receptor antagonist (IL-1ra), IL-8, and cortisol. Muscle was analyzed for glycogen content and relative gene expression of 13 cytokines (IL-1alpha, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, IFN-gamma, TNF-alpha) by use of real-time quantitative RT-PCR. Significant but modest increases were measured for plasma IL-6, IL-10, IL-1ra, and IL-8, but the pattern of increase did not differ between CHO and Pla groups. The rate of decrease in muscle glycogen content did not differ between CHO and Pla (P = 0.463). Muscle cytokine mRNA was detected preexercise for IL-1beta, IL-6, IL-15, IL-8, and TNF-alpha, and of these, IL-1beta, IL-6, IL-8, and TNF-alpha were significantly increased after the 2-h weight training bout. The increase in mRNA (fold difference from preexercise) did not differ between CHO and Pla groups. In summary, CHO vs. Pla ingestion did not alter modest increases measured for plasma IL-6, IL-10, IL-1ra, and IL-8, and muscle gene expression for IL-1beta, IL-6, IL-8, and TNF-alpha in strength-trained subjects lifting weights intensively for 2 h.

Influence of surface carbon coverage of C1 (TMS) stationary phases on the separation of nonylphenol ethoxylate ethoxymers.

The determination of surfactants in surface waters is required owing to their toxicity to aquatic micro-organisms and potential as endocrine disrupters. We have previously reported a method for the simultaneous separation of linear alkyl benzene sulfonates (LAS) and nonylphenol ethoxylates (NPEO) by high-performance liquid chromatography using a C1 (TMS) column. In this earlier work we discussed some problems with the resolution of individual ethoxymers from NPEO using C1 columns from different manufacturers. Here, we postulate that this phenomenon may be linked to carbon coverage of the C1 (TMS) stationary phases and study this utilising both elemental (bulk) analyses and surface specific analyses by X-ray photoelectron spectroscopy. Data obtained indicate that for the simultaneous separation of the LAS homologues and ethoxymers of NPEO, the stationary phase must have some trimethylsilyl groups bound to the surface of the silica in order to achieve separation of the LAS homologues, however the degree of surface coverage must not be greater than ca. 0.5 micromol/m2 in order to achieve adequate resolution of the NPEO ethoxymers. These data support earlier evidence for a "pseudo" reversed-phase mechanism for this separation.

Effects of acid treatment on the trace metal content of chromatographic silica: bulk analysis, surface analysis and chromatographic performance of bonded phases.

A series of studies has been carried out on the effect of refluxing silica chromatography particles for 0.5 h and 18 h in water, dilute hydrochloric acid and dilute hydrofluoric acid. The bulk and surface trace metal concentrations were measured by inductively-coupled plasma atomic emission spectroscopy, static secondary ion mass spectrometry (SSIMS) and X-ray photoelectron spectroscopy. Diffuse reflectance Fourier transform infrared spectroscopy was used to determine changes in 'isolated" and "bonded" silanol groups. The chromatographic behaviour of a series of weakly basic analytes was investigated on C8 and C18 bonded phases manufactured from the acid-treated silicas. The different reflux treatments all resulted in a reduction in the numbers of isolated silanols compared with the untreated silica and SSIMS analysis suggested that the HF-treated silicas had undergone a more efficient surface rehydroxylation. Bulk trace metals were removed most effectively by the HF treatment, with the multivalent elements (Ti and Al) being the most difficult to remove. Surface specific analysis suggested that trace metals were removed more rapidly from the surface of the silica compared to the bulk matrix and that the acid treatments resulted in halide contamination of the silica surface. Evidence is presented to suggest that the bulk metal content of the silica is not representative of the concentration of metals at the chromatographic surface. The chromatographic investigations showed that the HF-treated silica gave substantially better performance towards weak bases than the HCl-treated silicas.

Towards an epidemiology of health: a basis for planning community health programs.

Raising the quality of life of a community is the ultimate goal of most health promotion programs. Yet such programs are commonly restricted to reducing known risks to health. It is suggested that this linkage of health promotion to disease prevention is self-defeating, and that health promotion needs community recognition and a suitable methodology of its own. To this end the traditional epidemiology of disease is extended to a potential epidemiology of health. A five-part analysis of health issues is then suggested as a basis for planning and evaluating community health programs.

Assessment of techniques for measuring contrast sensitivity in children.

Contrast sensitivity was measured in 10 children aged from 3 to 11 years using 4 psychophysical techniques in order to establish the best method of measurement for clinical use. Of the four methods, staircase, ascending continuous, modified Von Bekesy and two-alternate forced-choice, the staircase was selected as the most appropriate clinical technique and monocular contrast sensitivity functions of normal children were measured.

From Ottawa, Uppsala, and Alma-Ata to Canberra, Australia: a rationale for a degree in health.

The paper describes the principles of curriculum design applied in establishing the Degree of Bachelor of Applied Science in Health Education in Canberra, Australia in 1979. The design was based explicitly on three major initiatives in health planning and policy in the last decade: (i) the recommendations to the Canadian Government proposed by Lalonde in 1974, commonly called the Health Field Concept; (ii) the World Health Organization definition of Health, first stated in 1948, and reissued at Uppsala in 1977; and (iii) the World Health Organization policy statement from the Alma-Ata Seminar in 1978, which included social planning and legislative action among the legitimate concerns of health services. The authors, who are at present teaching the integrated units of the degree, describe the principal components, namely content, theoretical principles, professional skills and methods of knowledge integration which they are using to develop graduates who may be considered wither health educated or health educators. In either case, the program is intended to produce people who can provide a health development arm for, on the one hand, social planning and social change, and on the other, health-care services.

OKN asymmetries and binocular function in amblyopia.

Asymmetrical optokinetic nystagmus (OKN) means that OKN has a lower gain (slow-phase eye velocity/stimulus velocity) for monocular temporalward than nasalward visual field motion. OKN tends to be asymmetric in amblyopia, leading to suggestions of a link between OKN asymmetry and binocularity in the literature. The present study measured OKN in 13 amblyopes and five normal subjects. In an attempt to identify those binocular cells used in the OKN response, the degree of OKN asymmetry was compared with binocularity assessed by two different techniques: (1) stereopsis and (2) interocular transfer of threshold elevation (IOT). Horizontal monocular OKN was recorded for three different stimulus velocities in each subject. All the amblyopes were found to be stereoblind, although three amblyopes showed OKN asymmetries close to those found for the normal group. More association was seen between interocular transfer of the threshold elevation and OKN asymmetry; not all amblyopes demonstrated reduced IOT, but those amblyopes with no IOT all had OKN asymmetries more than 125% of the mean of the normal group. However, no association was seen between the amount of OKN asymmetry and the degree of IOT. The results are discussed in terms of the role of different groups of binocular neurones for OKN and the effect of the sensitive periods of development on these binocular neurones.

The use of computerized contrast sensitivity, Arden gratings and low contrast letter charts in the assessment of amblyopia.

Contrast sensitivity measured with an electronic display was compared with Arden gratings and low contrast letter charts in normal and amblyopic children and adults. The low contrast letter charts and the Arden gratings used in the conventional manner revealed no additional information over that obtained by conventional Snellen acuity. However, the interocular differences found with each plate of the Arden gratings compared favourably with the computerized CSF. With the addition of an extra plate to test at a higher spatial frequency, the Arden gratings would be a useful technique for monitoring amblyopia therapy.

Postpartum haemorrhage--a continuing problem.

The factors responsible for postpartum haemorrhage (PPH) in singleton vaginal deliveries, not complicated by a retained placenta, were identified by comparing labour characteristics in 86 women who had a PPH (blood loss greater than 500 ml) with 351 women whose blood loss at delivery was less than 350 ml. Primiparity, induction of labour by amniotomy/oxytocin, forceps delivery, long first and second stages, oxytocin compared with syntometrine (oxytocin plus ergometrine maleate), as a prophylactic oxytocic, were identified as significant risk factors. Epidural analgesia contributed indirectly to an increase in the risk of postpartum haemorrhage. The changes in labour ward practice over the last 20 years have resulted in the re-emergence of PPH as a significant problem.

Surface glycoproteins as markers of the cellular status of B chronic lymphocytic leukaemia lymphocytes.

The phenotype of B CLL cells is investigated with respect to their surface glycoproteins. These glycoproteins are identified by vectorial tritiation followed by 1 and 2 dimensional gel electrophoresis, and by lectin and MoAb binding using immunoprecipitation and flow cytometry. The profiles of the CLL cells are compared with those of normal B cells, prepared from tonsils, and T cells from peripheral blood. The CLL cells show many similarities with T cells, particularly the expression of glycoproteins which bind the MoAbs gpL 115, F10-44-2 and EZB 52, and a complex set of binding sites for Helix pomatia lectin. The significance of these observations in terms of the cellular origins of the leukaemic lymphocytes is discussed.

Molecular epidemiology of a parainfluenza type 3 virus outbreak on a pediatric ward.

Parainfluenza type 3 virus (PIV-3), an important cause of acute lower respiratory illness in children, can be transmitted nosocomially. To differentiate between nosocomial transmission and community-acquired infection, a polymerase chain reaction-based sequencing assay was developed for the 5' noncoding region of the PIV-3 fusion protein gene and was applied to virus specimens from 10 children infected with PIV-3 during a hospital outbreak. Four strains of PIV-3 were identified among the 10 virus isolates. Six isolates, which appeared to belong to 1 strain, were obtained from a cluster of nosocomial cases in a pediatric intermediate care unit. In contrast, the remaining 4 isolates, which appeared to belong to 3 different strains, were obtained from children infected in the community or elsewhere in the hospital. These data indicate that multiple strains of PIV-3 can be found during a single epidemic and provide evidence that infections within the intermediate care unit were probably caused by transmission of 1 strain of virus within the unit rather than reintroduction of virus by new patients or staff.

Characterization of a range of alkyl-bonded silica HPLC stationary phases: correlation of quantitative surface analysis data with the retention behavior of neutral, acidic, and basic solutes.

An investigation was made of the correlation between quantitative surface analytical data obtained by XPS and static SIMS and the chromatographic performance of a range of n-alkyl-bonded silica (C1-C18) packing materials. A series of acidic, basic, and neutral solutes was used to study the retention behavior. For comparison, analysis of bulk total percentage carbon (%C) and alkyl surface density of the bonded silica particulates were also included. Significant correlations were observed, in the majority of cases, between the retention factor (k) and the XPS C:Si atomic ratio, which was similar to that obtained between k and the bulk %C or k and the bonded alkyl chain length. Similar significant correlations were also obtained between k and the static SIMS alkyl:Si ion peak area ratios. XPS alkyl:Si atomic ratios were calculated as an estimate of alkyl surface coverage of the silica support, and these correlated well with the surface density calculated from the bulk %C and the surface area of the packing material. The XPS alkyl:Si ratio also demonstrated a significant correlation with the peak asymmetry factor derived for basic solutes. These studies confirm that both XPS and static SIMS can generate surface chemical data from chromatography particulates, which has direct relevance to the prediction of chromatographic behavior. We believe that these techniques will prove to be effective tools to assist in the characterization of chromatographic supports and stationary phases.

Feto-maternal consequences of high-dose glucose infusion during labour.

The effects on the fetus of high doses of glucose given to the mother in labour to correct maternal ketonuria were investigated. Three groups of patients were compared: one group received 1 litre of 10% (w/v) glucose intravenously over 1 h, the second group received 1 litre of 0.9% sodium chloride solution intravenously over 1 h and the final group had no supplementary infusion. It was observed that whereas glucose administration rapidly corrected maternal ketonaemia, there was a significant fall in pH and a rise in lactate in fetal blood. These effects were not observed in the other two groups. It was concluded that the use of high doses of intravenous glucose in labour should be avoided.

Recurrent mutations in haemophilia A give evidence for CpG mutation hotspots.

Haemophilia A is a common disorder of blood coagulation caused by a deficiency of factor VIII. It is inherited as an X-linked recessive trait, and one-third of all cases are thought to result from de novo mutations. The clinical severity of haemophilia A varies markedly among different families and a subset of the patients with severe disease develop antibodies against factor VIII, called inhibitors. Because of this heterogeneity, it is likely that many different molecular lesions result in haemophilia A. Indeed, of the nine mutations described to date, all appear to be unique changes. However in this study of 83 patients with haemophilia A we have identified two different point mutations, one in exon 18 and one in exon 22, that have recurred independently in unrelated families. Each mutation produces a nonsense codon by a change of CG to TG, and each occurred de novo on the X-chromosome donated by the maternal grandfather. These observations strongly support the view that CpG dinucleotides are mutation hotspots.

An extremely polymorphic locus on the short arm of the human X chromosome with homology to the long arm of the Y chromosome.

A genomic DNA clone named CRI-S232 reveals an array of highly polymorphic restriction fragments on the X chromosome as well as a set of non-polymorphic fragments on the Y chromosome. Every individual has multiple bands, highly variable in length, in every restriction enzyme digest tested. One set of bands is found in all males, and co-segregates with the Y chromosome in families. These sequences have been regionally localized by deletion mapping to the long arm of the Y chromosome. Segregation analysis in families shows that all of the remaining fragments co-segregate as a single locus on the X chromosome, each haplotype consisting of three or more polymorphic fragments. This locus (designated DXS278) is linked to several markers on Xp, the closest being dic56 (DXS143) at a distance of 2 cM. Although it is outside the pseudoautosomal region, the S232 X chromosome locus shows linkage to pseudoautosomal markers in female meiosis. In determining the X chromosome S232 haplotypes of 138 offspring among 19 families, we observed three non-parental haplotypes. Two were recombinant haplotypes, consistent with a cross-over among the S232-hybridizing fragments in maternal meiosis. The third was a mutant haplotype arising on a paternal X chromosome. The locus identified by CRI-S232 may therefore be a recombination and mutation hotspot.

The retroverted gravid uterus and its effect on the outcome of pregnancy.

Among 1954 pregnant women who booked before the end of the 14th week of gestation the uterus was retroverted in 220 (11.2%). The incidence of bleeding in early pregnancy and spontaneous abortion was significantly higher in the retroverted group. Only three patients (1.4%) with a retroverted gravid uterus developed acute retention of urine. Patients with retroverted uteri did not have a higher incidence of previous infertility, nor any increase in the incidence of common obstetric abnormalities.