25-year experience in the management of invasive bladder cancer by radical cystectomy.
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Biomedical subjects
Publications and source records attributed to P Jones.
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Mannitol is often included in the priming solution of the heart-lung machine used during cardiopulmonary bypass (CPB). This study was set up to evaluate the effect of different doses of mannitol on human patients. Patients receiving 10 g of mannitol (n = 18) had an increased diuresis only during the bypass period (mean time = 87 min) when compared with a control group (n = 19) who did not receive mannitol. Patients receiving 20 g of mannitol (n = 19) had a significantly greater diuresis than both the control group and the 10 g group and the diuresis continued on throughout the immediate postbypass period (total mean time approximately 3 h). Patients receiving 30 g of mannitol (n = 20) also had a significantly greater diuresis that continued on during the first hour in the intensive care unit (ICU) (total mean time approximately 4 h). After 6 h in the ICU, all three groups of mannitol-treated patients equally demonstrated a trend towards an increased diuresis over the control group, which became a significant increase by 12 h in the ICU (p = 0.001) despite indications that the mannitol had been cleared from the body. These results suggest that there is an improvement of renal function post-CPB if mannitol is included in the CPB prime which may be due to an amelioration of the ischaemic effects of bypass on the kidneys.
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We report here the results of a randomized double blind trial comparing coartemether (CGP56697), a combination of artemether and benflumetol, with pyrimethamine/sulfadoxine (P/S). Two hundred eighty-seven children 1-5 years of age with uncomplicated falciparum malaria were enrolled at two centers in The Gambia between July 1996 and December 1996. Following treatment, children were visited at home every 24 hr until a blood film free of asexual parasites was obtained. Genotyping of parasites was used to distinguish recrudescence from new infections. Three days after the start of treatment, 133 (100%) of the CGP56697-treated children compared with 128 (93.4%) of children treated with P/S had cleared their parasites (P = 0.003). The day 15 cure rate was 93.3% for CGP56697 and 97.7% for P/S (P = 0.13). Within the third and fourth week after initiation of therapy, 20 children treated with CGP56697 and one of the P/S-treated children returned with second malaria episodes (P < 0.0001). Genotyping suggested that the majority (19 of 23 [82.6%]) of these second episodes were due to new infections, supporting the World Health Organization recommendation that longer follow-up is not relevant for the assessment of drug efficacy. At the two-week follow-up, 28.9% of the P/S treated children but none of the CGP56697-treated children carried gametocytes (P < 0.0001). This study showed that CGP56697 is safe in African children with acute uncomplicated falciparum malaria, clears parasites more rapidly than P/S, and results in fewer gametocyte carriers. More frequent new infections within the third and fourth week following treatment with CGP56697 than treatment with P/S are likely to be due to the short prophylactic effect of CGP56697.
We undertook a survey of 2555 outpatients (both new and review) to look at the reasons for high non-attendance (DNA) rates. Completed questionnaires (n = 983, 38.5% response) indicated the main reasons: forgetting or not receiving the appointment because of illness, and less often because of feeling better; transport problems; and short notice. Our remedial actions included improving the clerical system, announcing DNA rates on a regular basis in GP surgeries and in the outpatient department, introducing a tear-off slip with the appointment letter for patients to return, installing a free answerphone, active GP/consultant involvement in DNA-related problems and local publicity campaigns. A new scheme in our trust--outpatient telephone follow-up--may also help in reducing DNA rates.
In HOLON, user clients, applications, data servers, and fine-grained elements are all objects in a document library. To that end, this paper reviews the past year of progress and lessons learned in HOLON for integrating the Web, HL7, CORBA, Arden, KQML, UMLS Thesaurus, and other standards to determine if object technology reduces common problems in document-centric libraries such as indexing, searching/retrieving, complex data type management, and maintenance, among others.
One of the deliverables of the HOLON (Health Object Library Online) project is the specification of a reference architecture for clinical information systems that facilitates the development of a variety of discrete, reusable software components. One of the challenges facing the HOLON consortium is determining what kinds of components can be made available in a library for developers of clinical information systems. To further explore the use of component architectures in the development of reusable clinical subsystems, we have incorporated ongoing work in the development of enterprise terminology services into a Problem List subsystem for the HOLON testbed. We have successfully implemented a set of components using CORBA (Common Object Request Broker Architecture) and Java distributed object technologies that provide a functional problem list application and UMLS-based "Problem Picker." Through this development, we have overcome a variety of obstacles characteristic of rapidly emerging technologies, and have identified architectural issues necessary to scale these components for use and reuse within an enterprise clinical information system.
Recent evidence that DNA from bacteria causes polyclonal activation of mouse B cells raises the question of whether DNA from other organisms has similar properties. Extending prior studies on bacteria and insects, we show here that the capacity of DNA to stimulate B cells correlates closely with hypomethylation of DNA CpG dinucleotide motifs. Thus strong stimulation of B cells was seen with DNA from various organisms displaying little or no methylation of CpG motifs, i.e., yeast, nematodes, and molluscs in addition to bacteria and insects. For these organisms, DNA induced nearly all B cells (including small resting B cells) to up-regulate the activation marker, CD69, and caused many B cells to enter the cell cycle, indicative of polyclonal activation; this effect was not seen after selective methylation of CpG motifs (tested on yeast DNA). By contrast, no stimulation of B cells was seen with DNA from organisms whose CpG motifs are heavily methylated, i.e., various vertebrates (mammals, fish, and frogs) and plants (corn). Despite this correlation, DNA prepared from two murine cell lines exhibiting hypomethylation of CpG motifs caused little or no stimulation of B cells. Thus, the idea that the stimulatory properties of DNA correlate solely with the presence of unmethylated CpG motifs may be an oversimplification.
An increased rate on non-righthandedness and other abnormalities of lateralization have been reported in schizophrenia. We investigated childhood hand preference and eye dominance as risk factors for adult schizophrenia among a general population birth cohort. Pre-schizophrenic children showed a significant excess of left-eye dominance at age 11 when compared with controls (OR 2.5, 1.0-5.8, p = 0.03), but there was no significant difference in hand preference between pre-schizophrenic children and controls.
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The fusion domain of human immunodeficiency virus (HIV-1) envelope glycoprotein (gp120-gp41) is a conserved hydrophobic region located at the N terminus of the transmembrane glycoprotein (gp41). A V2E mutant has been shown to dominantly interfere with wild-type envelope-mediated syncytium formation and virus infectivity. To understand this phenomenon, a 33-residue peptide (wild type, WT) identical to the N-terminal segment of gp41 and its V2E mutant were synthesized, fluorescently labeled, and characterized. Both peptides inhibited HIV-1 envelope-mediated cell-cell fusion and had similar alpha-helical content in membrane mimetic environments. Studies with fluorescently labeled peptide analogues revealed that both peptides have high affinity for phospholipid membranes, are susceptible to digestion by proteinase-K in their membrane-bound state, and tend to self- and coassemble in the membranes. In SDS-polyacrylamide gel electrophoresis the WT peptide formed dimers as well as higher order oligomers, whereas the V2E mutant only formed dimers. The WT, but not the V2E mutant, induced liposome aggregation, destabilization, and fusion. Moreover, the V2E mutant inhibited vesicle fusion induced by the WT peptide, probably by forming inactive heteroaggregates. These data form the basis for an explanation of the mechanism by which the gp41 V2E mutant inhibits HIV-1 infectivity in cells when co-expressed with WT gp41.
BACKGROUND: Nocturnal mechanical ventilation (NMV) can reduce symptoms of hypoventilation and improve gas exchange in patients with chronic respiratory failure but there is no data concerning the impact of nocturnal mechanical ventilation on daily activity. We prospectively measured daily activity as judged by total steps per day. PATIENTS AND METHODS: Thirty stable patients (17 men, mean age 55.2 years, pCO2: 62.3 +/- 9.0 mmHg) with chronic respiratory failure. DIAGNOSIS: Kyphoscoliosis (n = 11), COLD (n = 7), neuromuscular diseases (n = 6), post-tbc sequelae (n = 6). Applying a pedometer over a 7 day period before and 3 months after initiating nocturnal mechanical ventilation the steps per day were counted. We also obtained arterial blood gases and applied the St. George's Respiratory Questionnaire (scoring range from 0 = complete health to 100 = worst possible). RESULTS AND CONCLUSIONS: The daily activity in patients with hypercapnic respiratory failure as judged by the total amount of steps per day increased by 120% after 3 months of nocturnal mechanical ventilation (from 1606.9 +/- 1341.3 to 3535 +/- 1813.8 steps per day, p < 0.0001). This was associated with a significant improvement in daytime blood gases and quality of life (QoL) as judged by questionnaire (total score: from 61.3 +/- 14.9 to 48.3 +/- 18.7, p = 0.0006). However no correlation between steps per day and QoL was found.
In a sample from the unselected, general population Northern Finland 1966 Birth Cohort, 11017 individuals alive at the age of 16 years were studied until the age of 27. The cumulative incidence of early onset schizophrenia until 23 years was higher (1.14%; 9/792) among young persons from the highest social class or class I (determined according to father's occupation) than among children from lower social classes (0.47%; 48/10225), the difference being statistically significant (p < 0.05). The incidence of schizophrenia in the highest social class was higher than expected among girls, firstborns, children of young mothers under 30 and urban residents (p < 0.05) compared with lower social classes. When cases from the highest and other social classes were compared, there was no clear difference in background factors or clinical course. Four alcoholics, one of them also schizophrenic, were found among nine social class I fathers. The results suggest that in some families in Northern Finland, a father's professional advancement, often linked to mental disorder, may be one determinant of an increased risk of schizophrenia in the child.
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Over a century ago, the Scottish psychiatrist Thomas Clouston proposed the idea of a developmental or adolescent insanity. He characterised the condition as having a male predominance and a poor outcome, and noted the frequency of a family history and of minor anomalies of the palate; he considered it a disorder of cortical development and the onset of psychotic symptoms due to maturation during adolescence "of certain parts of the brain which had lain dormant before". Clouston's idea was subsequently eclipsed by the broader dementia-praecox espoused by Kraepelin and Bleuler, but recent epidemiological, neuroimaging, and neuropathological research supports the existence, within the schizophrenia syndrome of a group of patients with a severe, early onset, developmental psychosis. This disorder, re-christened as neurodevelopmental schizophrenia, is associated with childhood language and speech difficulties which render subjects more likely to later misinterpret their own inner speech as external voices; like all developmental disorders of language, it is commoner in males. Predisposing factors include the inheritance of abnormal cerebral asymmetry, and early environmental hazards of brain development such as prenatal exposure to maternal viral infection and perinatal complications.
BACKGROUND: Recent evidence suggests that neurodevelopmental impairment may be a risk factor for later affective disorder. METHODS: Associations between childhood developmental characteristics and affective disorder were examined in a prospectively studied national British birth cohort of 5362 individuals born between March 3 and March 9, 1946. Mental state examinations by trained interviewers performed at ages 36 and 43 years identified 270 case subjects with adult affective disorder (AD). Teachers' questionnaires completed at age 13 and 15 years identified 195 case subjects who had shown evidence of childhood affective disturbance (CAD). RESULTS: Female gender and low educational test scores at ages 8, 11, and 15 years were a risk factor for AD, CAD, and AD without CAD. In addition, attainment of motor milestones was later in the CAD group (odds ratio [OR] = 1.2; 95% confidence interval [CI], 1.1-1.3), followed by, and independent of, greater risk for speech defects between the ages of 6 and 15 years (OR = 2.0; 95% CI, 1.3-3.0), decreased psychomotor alertness on medical examination between ages 4 and 11 years (OR = 4.6; 95% CI, 2.2-9.7), and an excess of twitching and grimacing motor behaviors in adolescence (OR = 3.9; 95% CI, 2.5-6.1). Persistent CAD was strongly associated with persistent AD (OR = 7.8; 95% CI, 2.6-23.2). CONCLUSION: The findings give credence to the suggestion that affective disorder, especially its early-onset form, is preceded by impaired neurodevelopment.
As a prerequisite to the use of the Finnish National Hospital Discharge Register in psychiatric epidemiological research, we studied the diagnostic reliability of the register in terms of the psychiatric morbidity experienced by a national birth cohort. We investigated all entries to the register for a sample based upon the Northern Finland 1966 birth cohort at the age of 16 years (n = 11017). Until the end of 1993 (age 27 years), a total of 563 subjects had a register diagnosis indicating a psychiatric illness, 37 of them being schizophrenia. When operational criteria (DSM-III-R) were applied to clinical information in the available original hospital records for cases of psychosis, personality disorder and substance abuse (n = 249), 71 fulfilled criteria for schizophrenia, including all of the 37 cases in the register and an additional 34 (48% false-negatives), most frequently diagnosed in the register as schizophreniform or other psychosis. Despite the official use of DSM-III-R nomenclature, it appears that the clinical concept of schizophrenia in Finland, manifest within the register, remains very restrictive. The application of operational criteria is a necessary prerequisite for scientific research on schizophrenia.