Biomedical subjects

C Paul

Publications and source records attributed to C Paul.

At least 55 records · Page 3Linked to original sources

PubMed2001

Prospective evaluation of the effects of prostatectomy on symptoms and quality of life.

AIMS: To evaluate prospectively urinary symptoms and quality of life before and after prostate surgery, among men who had been on a waiting list for elective transurethral prostate resection (TURP). METHODS: Face-to-face interviews with 47 men before and after prostate surgery using the urinary symptom specific American Urological Association Urinary Symptom Index (AUA-7), the Short Form 36 Health Survey (SF-36), and questions relating to the effects of urinary symptoms on men's lives and acceptable waiting times for surgery. RESULTS: The mean AUA-7 score before surgery for all participants was 22.2 (range 5-34) and after surgery improved to a mean of 7.3 (range 1-28). Men with severe urinary symptoms before surgery experienced the greatest improvement in symptoms after surgery, compared with the mild/moderate symptom group. Significant improvements occurred in three of the eight SF-36 dimensions following surgery. Acceptable waiting times for surgery differed according to the severity of mens' urinary symptoms. CONCLUSIONS: Efforts to develop methods for prioritisation of access to surgery are supported. Men with mild or moderate symptoms may reasonably delay surgery, with the expectation that, if they develop more severe symptoms, surgery will be helpful. Because of the risks as well as the benefits of prostate surgery, the use of illustrative vignettes may be useful for clinicians advising patients.

Activities of Daily Living↗

PubMed2001

Anti-mosquito midgut antibodies block development of Plasmodium falciparum and Plasmodium vivax in multiple species of Anopheles mosquitoes and reduce vector fecundity and survivorship.

The mosquito midgut plays a central role in the sporogonic development of malaria parasites. We have found that polyclonal sera, produced against mosquito midguts, blocked the passage of Plasmodium falciparum ookinetes across the midgut, leading to a significant reduction of infections in mosquitoes. Anti-midgut mAbs were produced that display broad-spectrum activity, blocking parasite development of both P. falciparum and Plasmodium vivax parasites in five different species of mosquitoes. In addition to their parasite transmission-blocking activity, these mAbs also reduced mosquito survivorship and fecundity. These results reveal that mosquito midgut-based antibodies have the potential to reduce malaria transmission in a synergistic manner by lowering both vector competence, through transmission-blocking effects on parasite development, and vector abundance, by decreasing mosquito survivorship and egg laying capacity. Because the intervention can block transmission of different malaria parasite species in various species of mosquitoes, vaccines against such midgut receptors may block malaria transmission worldwide.

Animals↗

PubMed2001

Revisiting the enzymes stored in the laticifers of Carica papaya in the context of their possible participation in the plant defence mechanism.

In the tropical species Carica papaya, the articulated and anastomosing laticifers form a dense network of vessels displayed in all aerial parts of the plant. Damaging the papaya tree inevitably severs its laticifers, eliciting an abrupt release of latex. Besides the well-known cysteine proteinases, papain, chymopapain, caricain and glycyl endopeptidase, papaya latex is also a rich source of other enzymes. Together, these enzymes could provide an important contribution to plant defence mechanisms by sanitising and sealing the wounded areas on the tree.

Amino Acid Sequence↗

PubMed2001

High prevalence of vasectomy in New Zealand.

The aim of this study was to examine the prevalence of vasectomy and associated factors in New Zealand, based on interviews with men. Participants were randomly selected from European men, aged between 40 and 74 years, on the general electoral roll. Telephone interviews were completed with 1225 men between 1997 and 1999. Overall, the prevalence of vasectomy was 44% (95% CI, 37-52%), adjusted to the age distribution of all New Zealand men aged 40-74 years. The prevalence ranged from 57% of men aged 40-49 years to 15% of those aged 70-74 years. Catholic men had a significantly lower odds of vasectomy, and there was a trend in increasing odds of vasectomy with increasing number of marriages and level of education of the wife. The results confirm a very high prevalence of vasectomy among New Zealand men. Comparison with earlier surveys based on interviews of women showed an increasing prevalence of vasectomy in each birth cohort from the 1920s to the 1950s. Vasectomy has been popular with men across all socioeconomic groups. New Zealand is an ideal country in which to study consequences of vasectomy.

Adult↗

PubMed2001

Pacifigorgianes and tamariscene as constituents of Frullania tamarisci and Valeriana officinalis.

The sesquiterpenoid constituents of the essential oils from the liverworts Frullania tamarisci, Frullania fragilifolia and of the angiosperm Valeriana officinalis were investigated. Tamariscene, a compound with a new sesquiterpene skeleton, valerena-4,7(11)-diene and five new pacifigorgiadienes, namely pacifigorgia-1,10-diene, pacifigorgia-1(6),10-diene, pacifigorgia-1(9),10-diene, pacifigorgia-2,10-diene, and pacifigorgia-2(10),11-diene were isolated and identified. Structure elucidation was carried out by NMR spectroscopy and chemical correlations to establish absolute configurations. Compounds present in both the essential oils of the Frullania species and Valeriana officinalis were enantiomeric to each other. A plausible biogenetic relationship between the pacifigorgiane, valerenane and tamariscane skeletons is postulated. Pacifigorgia-6,11-diene, not yet detected in nature, was generated by dehydration and rearrangement of natural (-)-tamariscol.

Magnetic Resonance Spectroscopy↗

PubMed2001

Sesquiterpenoid constituents of the liverworts Lepidozia fauriana and Lepidozia vitrea.

The sesquiterpene constituents of the essential oils of the Taiwanese liverworts Lepidozia fauriana and L. vitrea were investigated. 11,12-Dihydrochiloscyphone and 7,10-anhydro-11,12-dihydrochiloscypholone were isolated from L. fauriana and spectroscopically characterised together with their hydrogenation products. From the same species three amorphane derivatives amorpha-4,9-dien-14-al, amorpha-4,9-dien-2-ol and 7,14-anhydroamorpha-4,9-diene, and from L. vitrea two oxygenated elemanes, namely 7-acetoxy-elema-1,3-dien-8-ol and elema-1,3-dien-7-ol, were isolated and identified. Structure elucidation was carried out by NMR spectroscopy and chemical correlations in conjunction with enantioselective gas chromatography were utilized to establish absolute configurations.

Gas Chromatography-Mass Spectrometry↗

PubMed2001

Expression of topoisomerase IIalpha in the G0/G1 cell cycle phase of fresh leukemic cells.

Topoisomerase IIalpha (topo IIalpha) is the target enzyme for several antineoplastic drugs. Correlation between low expression of topo IIalpha and drug resistance has been shown in vitro, but there is limited evidence of a correlation to initial response to treatment or to overall prognosis. Normal cells express topo IIalpha in S/G2/M phase of the cell cycle but not in G0/G1 phase. However, some data suggest that topo IIalpha could be expressed in G0/G1 phase in malignant cells. We have investigated the expression of topo IIalpha in leukemic cells from 25 patients with acute leukemia by flow cytometry, separating cells of different cell cycle phases. We demonstrated that 9/25 samples showed >50% positive cells in G0/G1, and another five samples showed >20%. This finding could possibly provide an explanation to previous difficulties in correlating topo IIalpha expression with clinical outcome. Six of eight patients, where >20% of the cells in G0/G1 were positive for topo IIalpha, entered CR, compared to one of five patients with <20% topo IIalpha positive cells in G0/G1. We suggest that topo IIalpha expression in G0/G1 in leukemic cells may be of predictive value for clinical response to cytostatic drugs.

Acute Disease↗

PubMed2001

Lateralized cognitive deficits in children following cerebellar lesions.

The aim of this preliminary study was to examine the developing cognitive profiles of children with cerebellar tumours in a consecutive series of clinical patients. MRI and longitudinal intellectual profiles were obtained on seven children (two females, five males; mean age 3 years at diagnosis; mean age 7 years at first assessment). Tumours in three of the children were astrocytomas; of the remaining tumours, two were medulloblastomas, one low-grade glioma, and one ependymoma. In right-handed children, we observed an association between greater damage to right cerebellar structures and a plateauing in verbal and/or literacy skills. In contrast, greater damage to left cerebellar structures was associated with delayed or impaired non-verbal/spatial skills. Long-term cognitive development of the children studied tentatively supports a role for the cerebellum in learning/development. These findings suggest that lateralized cerebellar damage may selectively impair the development of cognitive functions subserved by the contralateral cerebral hemisphere and, in addition, that all children with cerebellar lesions in early childhood should routinely undergo long-term monitoring of their intellectual development.

Cerebellar Neoplasms↗

PubMed2001

Effects of arsenic trioxide (As2O3) on leukemic cells from patients with non-M3 acute myelogenous leukemia: studies of cytotoxicity, apoptosis and the pattern of resistance.

Arsenic oxide (As2O3) has recently been reported to induce remission in a high percentage of patients with acute promyelocytic leukemia (APL). The aim of this study was to investigate the effects of As2O3 at therapeutic concentrations on cell viability and apoptosis on leukemic cells from patients with non-M3 acute myelogenous leukemia (AML) and to study the resistance profile compared to conventional AML drugs. Cells from 20 patients were exposed to therapeutic concentrations of As2O3 continuously for 96 h. As2O3 reduced the viability in blast cells from all the 20 tested patients compared to unexposed controls (p-value: 0.02 at 0.05 microM; <0.005 at 1.0 microM and higher concentrations). An increase in the apoptotic rate was also seen after incubation with As2O3. Parallel to the incubation with arsenic the in vitro sensitivity to a number of chemotherapeutic agents commonly used in AML was studied. Correlation coefficients for the in vitro sensitivity were highly significant between the conventional AML drugs except for Ara-C. For As2O3, all the correlation coefficients were negative and ranged between -0.05 and -0.51. Furthermore, increased P-gp expression in a multidrug resistant HL-60 cell line did not decrease the sensitivity to As2O3 as compared to the parental cell line. Neither did a P-gp-transfected variant of the K562 cell line show decreased sensitivity to As2O3. We conclude that As2O3 at therapeutic concentrations induces apoptosis and cytotoxic effects in blast cells from patients with non-M3 AML, and that As2O3 differs from conventional AML drugs with respect to the mechanisms that confer resistance to the drugs.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2001

Measurement of fetal nuchal translucency thickness by three-dimensional ultrasound.

OBJECTIVE: To investigate the feasibility and repeatability of nuchal translucency thickness measurement using three-dimensional ultrasound. METHODS: Forty consecutive women with uncomplicated singleton pregnancies attending for Down syndrome screening at 11-14 weeks' gestation were included in this prospective crossover trial. Nuchal translucency thickness was measured using both two-dimensional and three-dimensional ultrasound. In each case two three-dimensional volumes were recorded and then examined by using the technique of planar reformatted sections. The initial plane of the first volume always contained a clear image of the nuchal region ('sagittal volume'), whilst the initial plane of the second volume was selected randomly regardless of fetal position ('random volume'). The repeatability of nuchal translucency measurement was examined by constructing a scatter diagram of the difference between the measurements plotted against the mean of two readings. RESULTS: Nuchal translucency measurements could be repeated in 38/40 (95%) sagittal volumes and 24/40 (60%) random volumes. The mean difference between two-dimensional measurements and those obtained by reslicing of sagittal three-dimensional volumes was -0.097 mm (95% limits of agreement from -0.481 to 0.675) and 0.225 mm (95% limits of agreement from -0.369 to 0.819) when random volumes were examined. CONCLUSIONS: Reslicing of stored three-dimensional volumes can be used to replicate nuchal translucency measurements only when nuchal skin can also be clearly seen on two-dimensional ultrasound.

Cross-Over Studies↗

PubMed2001

The new topical ascomycin derivative SDZ ASM 981 does not induce skin atrophy when applied to normal skin for 4 weeks: a randomized, double-blind controlled study.

BACKGROUND: SDZ ASM 981 is a selective inhibitor of inflammatory cytokines released from T lymphocytes and mast cells, which has been developed for the treatment of inflammatory skin diseases. OBJECTIVES: In the present study, the atrophogenic potential of SDZ ASM 981 1% cream in humans was compared with that of medium and highly potent topical steroids, and vehicle. METHODS: Four different preparations, SDZ ASM 981 1% cream, the corresponding vehicle of SDZ ASM 981 1% cream, betamethasone-17-valerate 0.1% cream and triamcinolone acetonide 0.1% cream, were applied to the volar aspect of the forearms of 16 healthy volunteers, twice daily, 6 days a week, for 4 weeks. Skin thickness was evaluated by ultrasound examination, clinical signs of atrophy by stereomicroscopy, and epidermal thickness was assessed by histology. RESULTS: Both topical corticosteroids induced a significant reduction in skin thickness, as compared with SDZ ASM 981 1% cream and vehicle, which were shown to be equivalent. The difference in skin thickness (measured by ultrasound examination) between patients treated with SDZ ASM 981 1% cream and those receiving either of the two topical steroids was significant from day 8 onwards. Histological analysis performed at day 29 showed significant epidermal thinning with topical steroids compared with SDZ ASM 981 1% cream or the vehicle. Conclusion The lack of atrophogenic properties of SDZ ASM 981 1% cream in this short-term study demonstrates its potential as long-term treatment for inflammatory skin diseases, thus overcoming a major drawback of topical steroids. This may also be important for the treatment of children, and sensitive areas of skin, such as the face and skin-folds.

Administration, Topical↗

PubMed2001

Quality of life and clinical outcome in psoriasis patients using intermittent cyclosporin.

BACKGROUND: Psoriasis causes considerable patient morbidity and can seriously affect a patient's quality of life (QoL). OBJECTIVES: To investigate the relationships between changes in QoL and measures of severity and extent of disease, and itch, in patients with chronic plaque psoriasis receiving intermittent short courses of cyclosporin (Neoral). METHODS: This study was performed as part of an international trial investigating the safety, efficacy and total costs of intermittent short courses of cyclosporin (the PISCES study). All patients received cyclosporin until clearance and were then followed up until relapse. On relapsing, patients received another course. Patients were followed up for a minimum of 1 year during which they could receive as many courses of treatment as necessary. In a subgroup (n = 255) of patients in the trial, the Dermatology Life Quality Index (DLQI) was used to assess the impact of psoriasis and its treatment on the patients' health status at the beginning and end of each treatment period. At the beginning and end of each treatment period, as well as at 2-weekly visits, the extent and severity of disease, together calculated into a modified Psoriasis Area and Severity Index (PASI), and itch were recorded. Data were analysed using the Wilcoxon matched pairs test, multivariate Hotelling's T2 tests, and Spearman's rank correlation coefficients (rs). RESULTS: During treatment, a clear impact on the overall DLQI scores and in the scores in all six DLQI headings was found (i.e. an improvement in QoL; P < 0.001 in all scores). Also, significant decreases in PASI and itch scores were found (P < 0.001). Multivariate analyses confirmed that a decrease in PASI and itch scores was accompanied by an impact on the DLQI scores during and between the two treatment periods (P < 0.0001). Statistically significant but weak correlations were found between changes in QoL and changes in PASI (rs = 0.40 and 0.24 for the first and second treatment periods, respectively) and itch scores (rs = 0.31 and 0.42, respectively). CONCLUSIONS: Intermittent short courses of cyclosporin clearly improve the QoL of the patients and decrease the extent and severity of disease and itch. Changes in clinical outcome scores are accompanied by changes in QoL. The weak correlations between changes in QoL and clinical measures may suggest that no clear relationship between QoL and clinical outcomes exists. However, due to the inclusion and exclusion criteria of the study, both QoL and clinical outcome measures do not show much variation among this homogeneous group of patients. As long as the relationship between clinical outcome parameters and measures of QoL is not completely clear, both measures of health should be considered in adequate, patient-orientated clinical decision making.

Adult↗

PubMed2001

Long-term efficacy of antifungals in toenail onychomycosis: a critical review.

BACKGROUND: Modern antifungal drugs achieve high mycological and clinical cure rates in onychomycosis of the toes, but little is known about the long-term evolution of the treated patients. OBJECTIVES: The aim of this review was to analyse the therapeutic results recorded more than 1 year after initiation of therapy. METHODS: We used two endpoints for the analysis: EP1 (the number of patients with negative mycology after follow-up, divided by the number of patients included at day 0, including all patients lost to follow-up), and EP2 (the number of patients with negative mycology after follow-up divided by the number of patients with negative mycology at week 48). Clinical cure rate (EPclin) was the number of patients clinically cured or with minimal residual lesions divided by the number of patients included at day 0. RESULTS: From a Medline search we identified 17 studies providing results beyond 48 weeks. Ketoconazole 200 mg d(-1) up to 1 year resulted in EP1 of 11% at 18 months, and EP2 of 43%. Griseofulvin 1 g d(-1) for 1 year allowed an EP1 of 43% at 18 months, and EP2 of 71%. The mean EP1 after fluconazole once weekly up to 1 year was 49% at 18 months, and EP2 was 91%. With itraconazole 200 mg d(-1) or 400 mg d(-1) for 1 week each month for 3-4 months, EP1 was 37% at 18 months, and 53% at 2 years; EP2 was 76% at 4 years. Terbinafine 250 mg d(-1) for 12-16 weeks achieved an EP1 of 62% at 18 months, 72% at 2 years, and 60% at 4 years; EP2 was 80% at 18 months, 81% at 2 years, and 71% at 4 years. In the only study planned to compare the long-term efficacy of terbinafine and itraconazole, EP1 at 18 months was significantly higher with continuous terbinafine than with intermittent itraconazole (66% vs. 37%, P < 0.001). The clinical cure rates were 21% at 60 weeks and 37% at 72 weeks with fluconazole. EPclin was 27% at 18 months and 35% at 2 years with itraconazole. EPclin was 48% at 18 months, 69% at 2 years and 50% at 4 years with terbinafine. CONCLUSIONS: Considering the stringency of the criteria we used, this critical review suggests that the long-term efficacy achieved with terbinafine is superior to that obtained with griseofulvin, ketoconazole, fluconazole or itraconazole.

Antifungal Agents↗

PubMed2001

Cross-resistance to cytosine arabinoside in a multidrug-resistant human promyelocytic cell line selected for resistance to doxorubicin: implications for combination chemotherapy.

The pyrimidine analogue cytosine arabinoside (AraC) is one of the most effective drugs used in the treatment of acute leukaemia. Overexpression of the multidrug resistance (MDR-1) gene and its product, P-glycoprotein (P-gp), is associated with cellular resistance to drugs, such as anthracyclines and vinca alkaloids. This resistance can be reversed by cyclosporine analogues or verapamil (ver). We investigated the in vitro cross-resistance to AraC in a doxorubicin-resistant HL60 cell line, with an elevated expression of the MDR-1 gene. The resistant clone showed an eightfold increased resistance to AraC and a two- to fourfold resistance to the other analogues, as measured by cytotoxicity test. There was no significant increase in the activity of 5'-nucleotidase or in the amount of deoxyribonucleotide pools between cell lines. We could, however, detect a reduction in deoxycytidine kinase (dCK) activity (30%, P = 0.021, using deoxycytidine as substrate) and the level of AraC triphosphates was significantly reduced in the resistant cells (70%, P = 0.009). When the cells were exposed to cyclosporin A (CsA) or the cyclosporine analogue PSC 833 (PSC) in combination with AraC, there was more extensive apoptosis, as measured by formation of oligonucleosomal DNA fragmentation and caspase-3-like activity, than with exposure to AraC alone. We also found an increased retention of AraC in the resistant cells when incubated with AraC in combination with CsA. Ver in combination with AraC, failed to increase apoptosis for the resistant cell line. Our data suggests that the resistance to AraC for the P-gp-expressing cells is a result of a reduction of dCK activity and an increase in efflux, the latter possibly depending on P-gp. A combination of CsA or PSC with AraC may improve the effect of AraC in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

A case of body stalk anomaly at 10 weeks of gestation.

We describe a case of body stalk anomaly which was diagnosed at 10 weeks of gestation on a dating scan. The fetus was visualized within the exocelomic cavity outside an apparently intact amniotic membrane. The fetus displayed multiple anomalies characteristic of body stalk syndrome including a skull and brain defect, abdominal wall defect, kyphoscoliosis and gross deformities of the lower limbs. These findings do not support early amniotic membrane rupture as the primary event in the pathogenesis of body stalk anomaly and indicate that the exocelomic location of the fetus may actually be one of the features of this complex developmental anomaly.

Abnormalities, Multiple↗

PubMed2001

Intermittent short courses of cyclosporine microemulsion for the long-term management of psoriasis: a 2-year cohort study.

BACKGROUND: Cyclosporine is effective in psoriasis, but long-term continuous therapy may be limited by renal impairment and hypertension. Intermittent short courses of treatment should minimize side effects and improve the risk-benefit ratio. OBJECTIVE: Our purpose was to assess the long-term efficacy and safety of intermittent short courses of the microemulsion formulation of cyclosporine (Neoral) in the management of chronic plaque psoriasis unresponsive to topical therapies. METHODS: In a multicenter open cohort study, 76 subjects were treated intermittently over a 2-year period. Patients with chronic plaque psoriasis were treated with cyclosporine until clearance of psoriasis or for a maximum of 12 weeks. Patients were then randomized into two groups. Group A stopped cyclosporine abruptly, whereas group B had the dose reduced by 1 mg/kg per day each week until cessation, which was within 4 weeks. On relapsing, patients received further courses of cyclosporine. Intermittent treatment was continued in this way for 2 years. RESULTS: There was no statistically significant difference in the percentage of time in remission during the 2-year period between patients randomized to stop cyclosporine abruptly (56.2%) and patients randomized to taper cyclosporine within 4 weeks (61.8%). The mean percentage of time that patients received treatment during the study was 40.5% for randomization group A, 46.2% for randomization group B, and 42.8% overall. The median time to relapse was 115.5 days after the first treatment course but became progressively shorter after multiple treatment courses. Mean blood pressure and serum creatinine levels did not show any clinically significant changes over time. CONCLUSIONS: This study indicates that intermittent short courses of cyclosporine are effective in patients with moderate to severe psoriasis for up to 2 years while improving the safety profile relative to continuous cyclosporine monotherapy.

Adult↗

PubMed2001

One week terbinafine 1% cream (Lamisil) once daily is effective in the treatment of interdigital tinea pedis: a vehicle controlled study. LAS-INT-06 Study Group.

Duration of therapy is an important factor determining patients' compliance in dermatomycosis clinical practice. We undertook a prospective, randomised, double-blind, parallel group study to investigate the efficacy and tolerability of once daily treatment with terbinafine 1% cream for 1 week, compared to its vehicle, in adult patients with interdigital tinea pedis. Efficacy was assessed in terms of mycological cure, total clinical signs and symptoms scores, and clinical response, 1 day and 1, 5 and 7 weeks after end of treatment. Terbinafine 1% cream was significantly more effective than its vehicle in achieving and maintaining mycological cure for 7 weeks: 91.4% vs. 37.1%, P < 0.001. Terbinafine was also significantly more effective than its vehicle in reducing total clinical signs and symptoms scores, and in achieving clinical response. We conclude that terbinafine 1% cream, applied once daily for 7 days, is an effective and well-tolerated treatment for interdigital tinea pedis in nonimmunocompromised patients. The short duration of treatment needed to achieve mycological cure has important implications for patient compliance and for control of infection within the community.

Administration, Cutaneous↗

PubMed2001

Cyclin A is a mediator of p120E4F-dependent cell cycle arrest in G1.

E4F is a ubiquitously expressed GLI-Krüppel-related transcription factor which has been identified for its capacity to regulate transcription of the adenovirus E4 gene in response to E1A. However, cellular genes regulated by E4F are still unknown. Some of these genes are likely to be involved in cell cycle progression since ectopic p120E4F expression induces cell cycle arrest in G1. Although p21WAF1 stabilization was proposed to mediate E4F-dependent cell cycle arrest, we found that p120E4F can induce a G1 block in p21(-/-) cells, suggesting that other proteins are essential for the p120E4F-dependent block in G1. We show here that cyclin A promoter activity can be repressed by p120E4F and that this repression correlates with p120E4F binding to the cyclic AMP-responsive element site of the cyclin A promoter. In addition, enforced expression of cyclin A releases p120E4F-arrested cells from the G1 block. These data identify the cyclin A gene as a cellular target for p120E4F and suggest a mechanism for p120E4F-dependent cell cycle regulation.

3T3 Cells↗