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Biomedical subjects

S Wright

Publications and source records attributed to S Wright.

At least 163 records · Page 9Linked to original sources

Communicating the diagnosis of motor neurone disease.

Communication of the diagnosis of motor neurone disease (MND) is a particularly difficult task for doctors in view of the poor prognosis and the lack of significant treatment. This study examined patients' views of being given the diagnosis and of how it was communicated. Fifty people who had been diagnosed with MND more than six months previously were interviewed about their experience of the diagnosis. The majority reported positive aspects of being told, especially having a label for their condition. The most frequently mentioned critical aspect of how they were told was the directness and clarity with which they were given the information. Patients were more critical if the diagnosis was worse than expected (as it was for most patients) and more satisfied if they felt they had been able to ask questions. There was no evidence that unsatisfactory communications were associated with later mood disturbance. A longitudinal study is recommended to overcome limitations in this cross-sectional design.

Adaptation, Psychological↗

A prospective clinical comparison of two intravenous polyurethane cannulae.

Tissue irritation, as evidenced by phlebitis, associated with Optiva (Johnson & Johnson Medical) and Insyte (Becton Dickinson) polyurethane cannulae was studied. The integrity of the cannulae on removal, the incidence of infection at the cannula site and the factors which influence phlebitis were also examined. One thousand and eight patients had a polyurethane cannula placed for induction of anaesthesia for cardiac surgery. After surgery, the cannula was examined every 24 hours. If evidence of phlebitis occurred, the cannula was removed and sent for culture. All remaining cannulae were removed at 72 hours and the site examined daily for a further three days. There were 503 Optiva and 505 Insyte cannulae studied. The distributions between the two cannulae with respect to patient characteristics, gauge of cannula, number of attempts and difficulty of insertion, cannula site and anaesthetist inserting were similar. The early removal rate for both groups was 47%. Overall phlebitis rate with Optiva was 31% and Insyte 33%. This difference is not statistically significant. The cumulative phlebitis rate increased with time but did not differ between the two types of cannulae. Minor tip distortion or shaft kinking of the cannulae occurred in 16.2% of Optiva and 23.5% of Insyte. This difference is statistically significant and may relate to the slightly more acute taper at the Optiva cannula tip. Both cannulae were similar in clinical performance.

Adolescent↗

Hodgkin's disease variant of Richter's syndrome: experience at a single institution.

Patients developing Hodgkin's disease (HD) after a diagnosis of chronic lymphocytic leukemia (CLL), are frequently included in a series of patients with Richter's syndrome (RS). We sought to determine the natural history of the association of CLL and HD. Over a 21 year period, 1374 patients with CLL have been registered in our computer data base. Seven cases of CLL and HD have been documented and confirmed. The median age of these patients was 71 years (range 44-77) and clinical features included male gender (86%), B symptomatology (86%), rapidly progressive lymphadenopathy (71%), prior CLL therapy (71%), advanced Ann Arbor stage (86%), marrow involvement with HD (43%), and autoimmune hemolytic anemia (29%). HD was documented by excisional lymph node biopsy in six cases and splenectomy in one. Mixed cellularity HD was shown in six and nodular sclerosis in one. Five of the biopsies revealed intervening areas consistent with small lymphocytic lymphoma. The Sternberg-Reed (SR) cells were CD15+ in 6/7 cases, and Ki-1+ in the 6 patients tested. CD45 and CD20 staining of the SR cells was nonreactive. The median time to development of HD was 45 months (range 0 to 96). The overall responses to different chemotherapy regimens was approximately 25% with only one CR. Six patients have died at 3, 9, 10, 13, 15 and 36 months and one patient is alive with progressive disease at 11 months. Our data suggests that CLL patients have a heightened risk for HD, features of advanced HD on presentation, and a poor response rate with short survival.

Adult↗

Anxiety in patients with symptomatic breast disease: effects of immediate versus delayed communication of results.

Immediate reporting of fine needle aspiration biopsy (FNAB) specimens has been introduced into many breast clinics; in others, women return to a later clinic to receive the result. This delay in communication of results may lead to elevated anxiety. This study compared anxiety levels in two groups having FNAB. One group received results at the initial clinic visit (n = 51), the other having delayed communication (n = 51). Anxiety was measured using the six-item short form of the Spielberger State-Trait Anxiety Inventory (STAI-SSF) and was administered before and after each consultation. Initial anxiety was high in both groups. Women with malignant results had higher post-communication anxiety compared with women with benign results. However, within the group with benign results (the vast majority), immediate communication was associated with a significantly greater fall in STAI-SSF scores from before to after the first consultation (U = 587.0; P < 0.02). There was no difference between the immediate and delayed communication among women with a malignant diagnosis (U = 26.0; P = 0.91). These results provide preliminary support for the more widespread introduction of a cytologist into breast clinics to allow immediate communication of results.

Anxiety↗

Degradation of lamin B1 precedes oligonucleosomal DNA fragmentation in apoptotic thymocytes and isolated thymocyte nuclei.

Chromatin condensation and nuclear envelope breakdown are characteristic features of apoptotic cell death, but the mechanisms underlying these phenomena have not been identified. Solubilization of nuclear lamin is responsible for both events in mitosis. In this work, we report that glucocorticoids stimulate rapid degradation of lamin B1 that occurs before oligonucleosomal DNA fragmentation in apoptotic thymocytes. Protease inhibitors and the Ca2+ buffering agent BAPTA-AM block lamin degradation and DNA fragmentation, indicating that the processes are regulated by similar or identical mechanisms. Incubation of isolated thymocyte nuclei with Ca2+ stimulates lamin degradation before the detection of oligonucleosomal DNA fragments. However, in contrast to lamin dissolution during mitosis and some other forms of apoptosis, glucocorticoid-induced degradation of lamin B1 in thymocytes is not accompanied by dephosphorylation-mediated activation of cdc2. Our results demonstrate that lamin degradation is an early feature of apoptosis in thymocytes and suggest that chromatin condensation and breakdown of the nuclear envelope may occur as a result of disruption of nuclear lamina architecture.

Animals↗

Differentiation between human and animal strains of Cryptosporidium parvum using isoenzyme typing.

Isoenzyme typing was used to study a number of oocyst isolates of Cryptosporidium parvum from different geographical locations and of human or animal origin. All isolates showed identical enzyme motility when glucose phosphate isomerase (GPI; 23 isolates tested) or lactate dehydrogenases (LDH; 20 isolates tested) was assayed. However, two isoenzyme forms were observed with phosphoglucomutase (PGM; 9 animal isolates showed one form, while 8/9 human isolates showed a second form) and hexokinase (HK; 4 human isolates showed one form and 6 animal isolates showed a second form). Thus, PGM and HK each exhibit 2 isoenzymes corresponding to 2 parasite populations associated with separate hosts. The data from this study, plus supportive evidence obtained by different methods and by independent researchers, lend support to the hypothesis that separate cycles of transmission of C. parvum may exist within human and animal hosts.

Animals↗

Does routine child health surveillance reach children most at risk of accidental injury?

BACKGROUND: There is currently an increasing emphasis on accident prevention as part of routine child health surveillance, which unlike opportunistic accident prevention has the potential to reach the whole population. However, non-attenders at routine child health surveillance may also be children at higher risk of accidental injury, as there is some evidence that non-attenders may be more likely to live in socio-economic disadvantage, which is a risk factor for accidental injury. METHODS: A case control study was carried out in one general practice in Nottingham with 253 cases and 243 controls, aged four years and under, obtained from the practice age-sex register. Cases were defined as children who had attended the accident and emergency department, the general practitioner or the practice nurse after an accidental injury at any time during their life. Controls were children who had not had a medically attended accidental injury. Attendance at routine child health surveillance, before the date of the case's accidental injury, was assessed by attendance at the eight-month hearing test, immunization status, child health clinic visits and home visits by the health visitor. RESULTS: There was no significant difference between cases and controls in attendance for the hearing test, or immunization status. Cases received significantly more home visits after adjusting for confounding variables (odds ratio 2.44, 95 per cent confidence intervals 1.28-4.66). CONCLUSIONS: These findings suggest that non-attenders at routine child health surveillance activities are not at an increased risk of medically attended accidental injury. They also suggest that health visitors can identify those children most at risk of accidental injury using criteria for classifying priorities in caseloads.

Accident Prevention↗

Short-term Lupron or danazol therapy for pelvic endometriosis.

OBJECTIVE: To compare the efficacy of a 3-month trial of leuprolide acetate (LA; Lupron; TAP Pharmaceuticals, Deerfield, IL) versus danazol (Danocrine; Scenofi Winthrup Pharmaceuticals, New York, NY) therapy on laparoscopically proven endometriosis. DESIGN: Endometriosis severity was assessed at the time of laparoscopy and patients were randomized to receive 0.1 mg SC LA (n = 22) or 800 mg danazol orally (n = 18) daily for 3 months. A second laparoscopy and/or laparotomy was performed to assess the change in the extent of endometriosis and for surgical therapy. SETTING: Private practice at a university-affiliated hospital. PATIENTS: Forty patients with mild, moderate, or severe endometriosis. Ten patients were excluded. INTERVENTION: Three-month treatment randomly assigned to either LA or danazol. MAIN OUTCOME MEASURES: Prospective measurement of American Fertility Society endometriosis scores and size of ovarian endometriomata before and after therapy via laparoscopy. RESULTS: The mean endometriosis score including adhesions decreased significantly from 36 +/- 4.9 to 29 +/- 5.0 (mean +/- SEM) with LA and from 34 +/- 6.4 to 29 +/- 6.5 with danazol. The mean laparoscopic endometriosis score not including adhesions decreased from 27 +/- 3.5 to 22 +/- 3.4 with LA and 22 +/- 3.5 to 19 +/- 3.1 with danazol. Seven of 18 (39%) endometriomata responded to LA and 6 of 15 (40%) endometriomata responded to danazol. CONCLUSION: We conclude that both danazol and LA will reduce endometriosis scores after a 3-month course of therapy. Larger clinical trials are needed to compare short courses of therapy with the more established 6-month trials. A 3-month versus a 6-month course of therapy offers obvious benefits including decreased cost and decreased side effects.

Danazol↗

High molecular weight DNA fragmentation: a critical event in nucleoside analogue-induced apoptosis in leukemia cells.

Cleavage of DNA into internucleosomal fragments is one of the characteristics of apoptosis. However, searches for in vivo evidence of nucleosomal DNA fragmentation in leukemia cells freshly obtained from patients during chemotherapy frequently failed to reveal nucleosomal multimers (DNA ladders). It is not clear whether this type of DNA cleavage is an essential event in drug-induced apoptosis and thus a denominator of cell killing, or whether the internucleosomal DNA fragments are merely the by-products of the apoptotic process. Here, we report our investigation into the role of DNA fragmentation in apoptotic cell death induced by anticancer nucleoside analogues, both in cell culture and in leukemia patients undergoing chemotherapy. Using a 5'-end DNA-labeling technique and pulsed field gel electrophoresis, we detected fragmentation of DNA in two distinct size classes, internucleosomal and high molecular weight (predominantly 50 kb) DNA fragments, in a human leukemia cell line exposed to the nucleoside analogues fludarabine and gemcitabine. We further demonstrated that the two types of DNA fragmentation were separate events, distinguishable by their requirements for Ca2+ and responses to phorbol ester treatment. The drug-treated cells underwent morphological changes of apoptosis even after internucleosomal DNA fragmentation was selectively inhibited by intracellular Ca2+ chelation, or by treatment with phorbol ester. In contrast, neither apoptotic morphology nor internucleosomal DNA fragmentation was observed when the high molecular weight DNA fragmentation was blocked by inhibition of nucleoside analogue incorporation into DNA. These results suggest that cleavage of DNA into large fragments may be an initial event that is critical for drug-induced apoptosis, whereas activation of a Ca2+-dependent endonuclease to cleave DNA at internucleosomal sites is not an absolute requirement for the execution of the apoptotic cell death program. Further studies of leukemic lymphocytes obtained from 9 patients with chronic lymphocytic leukemia during therapy with fludarabine revealed high molecular weight DNA fragmentation, which was correlated with a decrease of peripheral lymphocytes in 6 patients, whereas only 1 of the 15 patients evaluated for nucleosomal DNA fragments showed the DNA ladders. These results indicate that high molecular weight DNA fragmentation occurs in vivo, and may be correlated with the cytotoxic action of the anticancer drugs. Further study of the association of high molecular weight DNA fragmentation with clinical response to chemotherapy is warranted.

Antineoplastic Combined Chemotherapy Protocols↗

Human immunodeficiency virus type 1 tat directs transcription through attenuation sites within the mouse c-myc gene.

The regulation of transcriptional elongation plays a central role in the expression of a number of cellular and viral genes. For example, levels of c-myc RNA change during cellular proliferation and differentiation via alterations in transcriptional attenuation near the 5' end of the c-myc gene. The protein that regulates transcription through attenuation sites in c-myc has not been identified. However, a candidate protein of equivalent function exists in the human immunodeficiency virus (HIV) genome, where the transactivator Tat increases transcriptional elongation through the HIV LTR and coding sequences by interacting with the trans-acting-response (TAR) RNA stem-loop that is found at the 5' end of all viral transcripts. By placing TAR 3' to the P2 promoter of the mouse c-myc gene, we demonstrate that Tat can also direct read-through transcription in mouse c-myc in transfected HeLa cells. Thus we identified a viral transactivator whose cellular counterpart regulates transcriptional attenuation within c-myc and other proto-oncogenes.

Animals↗

Analysis of the influenza virus gene pool of avian species from southern China.

Although Southern China has been considered the epicenter of human influenza pandemics, little is known about the genetic composition of influenza viruses in lower mammals or birds in that region. To provide information on the molecular epidemiology of these viruses, we used dot blot hybridization and phylogenetic methods to study the internal genes (PB1, PB2, PA, NP, M, and NS) of 106 avian influenza A viruses isolated from a total of 11,798 domestic ducks, chickens, and geese raised in Southern China including Hong Kong. All 636 genes examined were characteristic of avian influenza viruses; no human or swine influenza genes were detected. Thus, influenza virus reassortants do not appear to be maintained in the domesticated birds of Southeast Asia, eliminating opportunities for further gene reassortment. Phylogenetic analysis showed that the internal genes of these viruses belong to the Eurasian avian lineage, supporting geographical separation of the major avian lineages. The PB1 genes were most similar to A/Singapore/57 (H2N2) and Hong Kong (H3N2) viral genes, supporting an avian origin for the recent human H2N2 and H3N2 pandemic strains. The majority of internal genes from avian influenza viruses in Southern China belong to the Eurasian lineage and are similar to viruses that have recently been transmitted to humans, swine, and horses. This study provides evidence that the transmission of avian influenza viruses and their genes to other species is unidirectional and that the transmission of mammalian influenza virus strains to domestic poultry is probably not a factor in the generation of new pandemic strains.

Animals↗

Patterns of Reactivity between a Panel of Monoclonal Antibodies and Forage Rhizobium Strains.

A panel of 11 monoclonal antibodies raised against vegetative cells of Rhizobium leguminosarum biovar trifolii or Rhizobium meliloti was tested by enzyme-linked immunosorbent assay for reactivity with 47 strains of R. leguminosarum biovar trifolii and 60 strains of R. meliloti. The goal of the study was to define the degree of specificity associated with each antibody and to gain an understanding of the amount of antigenic diversity found among the strains and between the species. Each antibody was tested against each Rhizobium strain in four forms: washed steamed cells, washed unsteamed cells, cell-free culture broth, and nodule squash material. Each antibody showed a different pattern of reactivity among the 107 strains. One of each of the antibodies developed against R. meliloti and R. leguminosarum biovar trifolii reacted in a highly specific manner with cells or antigen from the immunogenic strain only. Nine of the antibodies recognized secreted as well as cellular antigen from many of the strains. Analysis of patterns of reactivity between the 107 strains and the 11 antibodies separated the strains into 28 groups of which 12 were represented by one strain only.

Journal Article↗

Use of splenic ultrasound: a new wave for immune thrombocytopenic purpura.

AIMS: To examine whether a therapeutic dose of ultrasound waves, when directed through the thoracic wall to the spleen, would significantly affect the platelet count in patients with stable immune thrombocytopenic purpura (ITP). METHODS: Continuous ultrasound at 1 W/cm2 spatial average-time average (SATA) intensity for up to one minute/5 cm2 treatment field was well tolerated in 13 patients with ITP and one with non-Hodgkin's lymphoma. Five healthy controls were also similarly treated. Peak platelet increments occurred four to eight hours after ultrasound treatment in the ITP group (n = 16 treatments). RESULTS: The mean peak platelet increment was 6.25 x 10(9)/l with a 5% confidence interval of the mean (95% CI) of 3.32 to 8.93 x 10(9)/l (p = 0.0004). The mean peak platelet increment of normal controls was 6.6 (n = 5; 95% CI = -2.3 to 15.5; p = 0.21) and for sham treated patients it was 0.66 (n = 11; 95% CI = -1.5 to 2.8; p = 0.60). There was a significant inverse correlation between patient age in the ITP group and peak platelet increment (r = -0.60; p = 0.015). CONCLUSIONS: Splenic ultrasound is a novel approach to the treatment of ITP, and may find a place in its diagnosis or management.

Adult↗