Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes? Systematic review.

BACKGROUND: It is unclear whether more timely cancer diagnosis brings favourable outcomes, with much of the previous evidence, in some cancers, being equivocal. We set out to determine whether there is an association between time to diagnosis, treatment and clinical outcomes, across all cancers for symptomatic presentations. METHODS: Systematic review of the literature and narrative synthesis. RESULTS: We included 177 articles reporting 209 studies. These studies varied in study design, the time intervals assessed and the outcomes reported. Study quality was variable, with a small number of higher-quality studies. Heterogeneity precluded definitive findings. The cancers with more reports of an association between shorter times to diagnosis and more favourable outcomes were breast, colorectal, head and neck, testicular and melanoma. CONCLUSIONS: This is the first review encompassing many cancer types, and we have demonstrated those cancers in which more evidence of an association between shorter times to diagnosis and more favourable outcomes exists, and where it is lacking. We believe that it is reasonable to assume that efforts to expedite the diagnosis of symptomatic cancer are likely to have benefits for patients in terms of improved survival, earlier-stage diagnosis and improved quality of life, although these benefits vary between cancers.

Effects of prepartum dietary carbohydrate source and monensin on periparturient metabolism and lactation in multiparous cows.

Eighty-five multiparous Holstein cows were used in a completely randomized design with restrictions to evaluate the effects of prepartum carbohydrate (CHO) source and monensin on periparturient dry matter intake (DMI), blood parameters, and lactation performance of dairy cows. Dietary treatments were arranged in a 2 x 2 factorial arrangement with a conventional (CONV) dry cow diet and a nonforage fiber source (NFFS) dry cow diet not supplemented (-) or supplemented (+) with 330 mg/cow per d of monensin as a top dressing. The CONV diet contained 70% forage and the NFFS diet contained nonforage fiber sources such that 28% of the forage was replaced with cottonseed hulls and soyhulls. The experimental diets (CONV and NFFS) were fed throughout the entire dry period (for 60 d before parturition). Monensin was top dressed once daily starting 28 d (27 +/- 1.8 SD) before the expected calving date and continued until parturition. After parturition, all cows received the same lactating cow diet. During the last 28 d of gestation, cows receiving the NFFS diets prepartum had greater DMI (15.8 vs. 11.9 kg/d), DMI as a percentage of body weight (2.1 vs. 1.6% of body weight), plasma glucose (67.4 vs. 64.6 mg/dL), and serum insulin concentrations (0.59 vs. 0.45 ng/mL), and lower plasma nonesterified fatty acid concentrations (185 vs. 245 microEq/L) compared with cows receiving the CONV diets prepartum. Average milk production or composition during the first 56 d of lactation was not significantly affected by prepartum source of CHO, monensin, or their combination; however, there was a trend for the prepartum CHO source to affect milk production over time. Supplementation of monensin as a top dressing for 28 d prepartum had no effect on periparturient measurements. The prepartum diet did not affect postpartum DMI, blood glucose, nonesterified fatty acids, insulin concentrations, or liver triglyceride content. Results from this research demonstrated that partly replacing conventional dietary carbohydrate sources with NFFS, cottonseed hulls and soyhulls, in the dry cow diet improved or maintained the prepartum DMI and therefore enhanced the prepartum metabolic status, as indicated by key blood metabolite concentrations. This greater prepartum DMI may potentially increase milk production during early lactation.

Seasonal variation in the level of antifreeze protein mRNA from the winter flounder.

Livers from winter flounder collected at monthly intervals throughout the year were analyzed for their content of antifreeze protein mRNA. Putative mRNA was detected in liver RNAs from summer fish by liquid hybridization to kinetically purified antifreeze protein cDNA. These mRNA sequences were shown by Northern blot analysis to be of the same length as mature antifreeze protein mRNA isolated from winter fish, and were able to direct the incorporation of alanine into a translation product which comigrated with antifreeze preproprotein. The build-up of antifreeze protein mRNA levels in the autumn and their decline in the spring to summer levels were measured by liquid hybridization. These seasonal fluctuations match closely, but slightly precede, the rise and fall in plasma osmolality due to the presence of antifreeze protein. In mid-winter 0.5% of the total liver RNA is antifreeze protein mRNA, and although by late August the level of this mRNA has declined to 0.0007% of the total RNA, at no time during the summer is the mRNA undetectable. These results suggest that antifreeze protein production is more likely to be regulated by changing the rate of transcription of their genes than by switching them between active and inactive states.

Cloning and characterization of the aldA gene of Aspergillus nidulans.

We have cloned and sequenced the aldA (encoding aldehyde dehydrogenase) gene of Aspergillus nidulans. The gene contains two introns which are similar in size and structure to other fungal introns. The amino acid sequence of aldehyde dehydrogenase (497 residues) shows a significant level of homology with analogous sequences in other organisms. Comparison of the primary structure of the active sites of the mammalian cytosolic and mitochondrial enzymes shows that the Aspergillus enzyme closely resembles the mammalian mitochondrial enzyme. Analysis of the 5' non-coding region of the aldA gene shows a TATA-like sequence located 90 bp upstream from the initiation codon. Two messenger-RNA start points are located 36 and 42 bp upstream from the start codon.

In vivo and in vitro effects of mutagenesis of active site tyrosine residues of mercuric reductase.

X-ray crystal structure analysis of mercuric reductase suggested that the binding site for Hg2+ consisted of two tyrosine residues, Tyr264 and Tyr605, as well as two cysteine residues, Cys207 and Cys628. We have previously shown that mutagenesis of Tyr605 to Phe lowered the kcat of the enzyme 6-fold, whereas the same mutation of Tyr264 resulted in a reduction of 160-fold [(1993) Biochemistry 32, 7475-7478]. Tyr605 occupies the same position in mercuric reductase as the active site His residue in the related enzyme glutathione reductase. The mutation of Tyr605 of mercuric reductase to a His residue produced a 24-fold decrease in kcat and a 15-fold decrease in Km. The in vivo resistance to Hg2+ of E. coli strains carrying wild type or mutant merA genes correlated with the in vitro measurements of kcat/Km for mercuric reductase activity.

Establishment of a CSF bank.

A bank of well-characterized CSF has been established by collecting and storing (-70 degrees C) CSF samples remaining after completion of routine clinical studies. Over 1,700 individual patient samples were collected during a 12-month period. A database derived largely from information down-loaded from existing hospital-based systems includes the results of individual CSF laboratory studies, in addition to the patient age, primary diagnoses, and details of any malignancy. CSF control material is used to verify storage conditions. The CSF bank supplies investigators with CSF handled in a standardized manner for more precise investigation of CNS disease.

Short report: identification of a specific pattern of vascular endothelial growth factor mRNA expression in human placenta and cultured placental fibroblasts.

Reverse transcription and the polymerase chain reaction (PCR) were used to detect vascular endothelial growth factor (VEGF) mRNA in human placental tissue and cultured placental fibroblasts obtained during the first trimester of pregnancy. The primers for VEGF corresponded to areas in exon 4 and exon 8 of the VEGF gene. After one round of PCR three products, equivalent to VEGF121, VEGF165 and VEGF189, were detected within placental tissue and cultured placental fibroblasts. A further round of PCR revealed the presence of two more products equivalent to VEGF206 and VEGF145. Thus, in addition to the production of readily secreted forms of VEGF (VEGF121 and VEGF165), the placenta produces several transcripts expected to increase the growth factor pool of the extracellular matrix.

National epidemic of Lordsdale Norovirus in the UK.

BACKGROUND: In early 2002 reports of outbreaks of gastroenteritis reached unprecedented levels in the UK. Forty five Norovirus outbreaks were reported in January 2002. OBJECTIVES: The objective of the study was to determine whether the outbreaks were Noroviral in origin and if so whether they represented a homogeneous or heterogeneous collection of Noroviruses by applying EIA and sequence analysis to representative faecal samples. STUDY DESIGN: Faecal specimens were collected during the week of highest incidence from 21 outbreaks in a variety of health care settings including hospitals and nursing homes. The outbreaks occurred in geographically distinct regions of the UK and samples were collected by reference laboratories in Glasgow, Manchester, Bristol and Southampton. RESULTS: The samples were all positive for Noroviruses by negative stain electron microscopy (EM) and Lordsdale virus (LV) EIA, therefore reverse transcriptase polymerase chain reaction (RT-PCR) amplification and nucleotide sequencing of the Norovirus RNA polymerase gene was performed on amplicons from samples of each of the 21 outbreaks to investigate the nature and extent of diversity. All samples were very closely related to the reference Lordsdale virus genome sequence. LV was first discovered during an hospital outbreak of gastroenteritis in Southampton General Hospital in March 1993. CONCLUSIONS: Noroviruses are a major cause of outbreaks of gastroenteritis in health care settings. LV is the predominant Norovirus in the UK and was detected in outbreaks that occurred during the national peak of gastroenteritis reports in January 2002.

Control of red blood cell mass in spaceflight.

The effect of spaceflight on red blood cell mass (RBCM), plasma volume (PV), erythron iron turnover, serum erythropoietin, and red blood cell (RBC) production and survival and indexes were determined for six astronauts on two shuttle missions, 9 and 14 days in duration, respectively. PV decreased within the first day. RBCM decreased because of destruction of RBCs either newly released or scheduled to be released from the bone marrow. Older RBCs survived normally. On return to Earth, plasma volume increased, hemoglobin concentration and RBC count declined, and serum erythropoietin increased. We propose that entry into microgravity results in acute plethora as a result of a decrease in vascular space. PV decreases, causing an increase in hemoglobin concentration that effects a decrease in erythropoietin or other growth factors or cytokines. The RBCM decreases by destruction of recently formed RBCs to a level appropriate for the microgravity environment. Return to Earth results sequentially in acute hypovolemia as vascular space dependent on gravity is refilled, an increase in plasma volume, a decrease in hemoglobin concentration (anemia), and an increase in serum erythropoietin.

Central venous catheter infection caused by Moraxella osloensis in a patient receiving home parenteral nutrition.

We report the first case of a central venous catheter infection caused by Moraxella osloensis, which was successfully treated without catheter removal. The isolation, identification, and pathogenesis of this species are discussed. It is recommended that Moraxella isolates be identified to species in order to determine the relative pathogenic and opportunistic roles of the various Moraxella species. Our case also demonstrates that catheter sepsis caused by some Gram-negative organisms may be amenable to systemic antibiotic therapy without the necessity of catheter removal.

Gram-positive cell wall structure of the A3 gamma type in heliobacteria.

The amino acid composition and structure of the peptidoglycan from Heliobacillus mobilis was determined by one- and two-dimensional thin-layer chromatography of completely and partially hydrolysed cell wall preparations. The structure was found to be of the A3 gamma type, with L,L-diaminopimelate in position 3, D-alanine in position 4 and a glycine interpeptide bridge, as found in certain groups of Gram-positive bacteria including Clostridium perfringens and Nocardioides simplex. The presence of a Gram-positive type of cell wall in heliobacteria is consistent with their phylogenetic relationship to the 'low G + C' Gram-positive bacteria, as previously demonstrated by 16S rRNA sequencing.

Construction of an epitope vector utilising the diphtheria toxin B-subunit.

An immunogenic loop within the diphtheria toxin has been deleted from the B-subunit by a modification of the inverse polymerase chain reaction (IPCR) and replaced by a unique restriction endonuclease site. An oligonucleotide encoding an identified epitope sequence from the major outer membrane protein of Neisseria meningitidis of similar size and structure to that deleted has been introduced into the restriction site. Expression of the resulting chimeric B-subunit from Escherichia coli yielded a protein that was recognised by a panel of antibodies specific for the meningococcal epitope. Initial immunisation data suggest that this protein could elicit an antibody response against both diphtheria toxin and meningococcal proteins.

Amplification with molecular beacon primers and reverse line blotting for the detection and typing of human papillomaviruses.

A novel method for the detection and typing of human papillomavirus (HPV) was developed using molecular beacon primers. The method is based on the use of HPV-specific primers containing a hairpin loop structure in which fluorescent donor and quencher groups are held in close proximity such that fluorescence is quenched. Amplification of the target sequence results in the opening of the loop and the resulting fluorescence can be detected on a sequence detector system (SDS) 7700 (Applied Biosystems), as used for TaqMan assays. Fluorescent amplicons were identified on the SDS 7700 and then typed by a single hybridisation with specific probes immobilised in lines on a nylon membrane and detected on a fluorescent scanner. This novel beacon primer method compared well with conventional PCR for cervical scrape specimens. The combination of the beacon primer method and reverse line blotting should enable large-scale population studies of HPV infection.

Progesterone up-regulates WT1 mRNA and protein, and alters the relative expression of WT1 transcripts in cultured endometrial stromal cells.

OBJECTIVE: To determine the change in expression of the Wilms tumor suppressor gene product, WT1, by progesterone alone in endometrial stromal cell culture and to study its relationship with prolactin, a marker of decidualization. In addition, to examine the change in ratio of WT1 isoforms with and without exon 5 message. METHODS: Endometrial biopsies were taken from eight patients who had hysterectomy. Stromal cells were isolated and cultured in the presence of progesterone alone (12 days) or progesterone and 8-bromo-cyclic adenosine monophosphate (cAMP) (6 days). RNA was extracted from cells, and reverse transcription, real-time polymerase chain reaction (PCR), and conventional PCR were done to analyze WT1 mRNA expression. Immunocytochemistry was performed on equivalent cells to study WT1 protein expression. Decidualization was identified by increased prolactin concentrations in the media and immunocytochemical markers IGFBP-1 and collagen IV. RESULTS: Reverse transcription and real-time PCR revealed a significant increase in WT1 mRNA with increasing progesterone concentrations when decidualization was occurring (n = 6, P =.002). Increasing progesterone concentrations also increased the proportion of the WT1 transcript containing a 17-amino-acid insert (+ exon 5 expression); changes in WT1 exon 5 expression have been shown to be involved in control of proliferation and differentiation. Significant correlations between WT1 message and prolactin existed at physiologic progesterone concentrations (6.25, 12.5, 25, and 50 nM; P <.05) until prolactin concentrations reached a plateau at 100 nM. At concentrations of progesterone alone (> 25 nM) and progesterone with 8-bromo-cAMP, WT1 protein was localized to the nuclei of many of the decidualized stromal cells. CONCLUSION: The changing expression of WT1 isoforms in endometrial stromal cells caused by progesterone may be important for differentiation into the decidualized phenotype.

Molecular epidemiology of trachoma in a Gambian village.

The application of a diagnostic and genotyping technique based on the polymerase chain reaction (PCR) to the study of trachoma epidemiology in the Gambian village of Jali is reported. PCR based on the major outer membrane protein (MOMP) gene of Chlamydia trachomatis appears to be more sensitive than either isolation or antigen detection by enzyme immunoassay; it had a specificity of 95% and sensitivity of 51% against clinical signs. PCR genotyping identified genotypes A and B of Chlamydia trachomatis circulating in Jali. Sequencing revealed a Pst1 restriction endonuclease site in the amplified MOMP gene of some B strains but not others; Pst1 digestion of the PCR product proved an easy method of distinguishing these strains. The distribution of serotypes and B strain variants shows a significant degree of household clustering (p < 0.001). PCR based genotyping combined with strain typing provides a new and powerful epidemiological tool for the study of transmission events in trachoma.

Psychological distress in survivors of residential fires.

This paper presents preliminary findings from an ongoing study of survivors of residential fires. The purpose of this study was to examine psychological distress and extent of loss in order to provide a psychological profile of survivors overtime. The sample (N = 69) was drawn consecutively from the database of residential fires available through the Philadelphia Fire Department. Levels of psychological distress were measured as well as reports of symptoms consistent with the diagnostic criteria for Post-traumatic Stress Disorder. The major findings indicate that residential fires caused significant and sustained distress. An agenda for further research and for services to survivors of these fires is presented.

Characteristic archaebacterial 16S rRNA oligonucleotides.

A method of analyzing 16S rRNA catalog data has been developed in which groupings at various taxonomic levels can be characterized in terms of specific "signature" oligonucleotides. This approach provides an alternative means for evaluating higher order branching possibilities and can be used to assess the phylogenetic position of isolates that are poorly placed by the usual clustering procedures. This signature approach has been applied to forty archaebacterial catalogs and every oligonucleotide with significant signature value has been identified. Sets of specific oligonucleotides were identified for every major group on a dendrogram produced by cluster analysis procedures. Signatures that would establish between group relationships were also sought and found. In the case of the Methanobacteriaceae the clustering methods suggest a specific relationship to the Methanococcaceae. This inclusion is in fact supported by six strong signature oligonucleotides. However there are also significant numbers of signature oligonucleotides supporting a specific relationship of the Methanobacteriaceae to either the Halobacteriaceae or the Methanomicrobiaceae. Thus the placement of the Methanobacteriaceae is less certain than the usual dendrograms imply. The signature approach also was used to assess the phylogenetic position of Thermoplasma acidophilum which is found to be more closely related to the methanogen/halophile Division than to the sulfur dependent Division of the archaebacteria. This does not imply however that Thermoplasma acidophilum is properly regarded as being in the methanogen/halophile Division.

Moraxella atlantae bacteraemia in a patient with systemic lupus erythematosis.

We describe the first reported case of human infection caused by Moraxella atlantae (formerly known as CDC group M-3) and its successful treatment with intravenous cefuroxime. The isolation and identification of this species, as well as the pathogenesis of the infection, are discussed. It is recommended that isolates of Moraxella species be speciated so that the epidemiological characteristics and pathogenesis of the infections caused by the various species may be understood more completely.

Determinants of anticipatory nausea and anticipatory vomiting in adults receiving cancer chemotherapy.

There is a need for further empirical investigation of variables that may contribute to the occurrence of anticipatory nausea and/or anticipatory vomiting (AN/AV) in persons receiving cancer chemotherapy. The purpose of this study was to examine the relationship of AN/AV in adults receiving an initial course of cancer chemotherapy in an outpatient setting with the following set of variables: symptom distress, mood disturbance, stage of disease, sensitivity to conditioning cues, emetic potential of antineoplastic drugs, age, psychosocial stress, and ability to cope. Thirty-two percent of the sample developed anticipatory nausea. Multivariate statistics were used to examine the contribution of the variables to the prediction of AN/AV. Analysis of the data revealed that 53% of the variance accounted for was contributed by the following combination of variables: emetic potential of drug, level of symptom distress, mood disturbance, stress and ability to cope (p = .001). The total percentage of cases correctly classified was 88.3%. This combination of variables correctly classified 100% of patients who experienced anticipatory nausea (n = 15). Eighty-two percent of patients who did not experience anticipatory nausea and/or anticipatory vomiting (n = 28) were classified correctly.

Cultural awareness in the context of terminal illness.

While cultural awareness provides direction for planning effective nursing interventions at all stages of health and illness, this article specifically addresses applications for patients who are terminally ill. Professional nurses encounter unique challenges in caring for terminally ill patients. Assisting patients to achieve an "appropriate death" requires communication and collaboration among patients, family members, and professional caregivers. Since patients and their families represent many systems of complex beliefs and values, nurses must be aware of the impact of cultural pluralism on nursing assessment and intervention in terminal illness. Reordering priorities and redistributing resources have been identified as new approaches in caring for terminally ill patients and their families. Two concepts that cut across all cultural boundaries are loss and grief. Expressions of loss and grief take on a variety of forms among members of diverse cultures. It is critical that nurses recognize, understand, and respect each family's culture-specific patterns with regard to terminal illness. Understanding the culture will lead to the design of culturally appropriate nursing care for patients and families. Culture brokerage is defined as an act of translation, where messages, instructions, and belief systems are exchanged between cultural groups. This strategy has the potential to increase understanding among those with diverse cultural backgrounds, resulting in increased patient/family satisfaction within the supportive care setting. Consonance between patients' needs and nurses' understanding of those needs will lead to more culturally appropriate intervention strategies.