PubMed Health⌕ Search

Biomedical subjects

C Wells

Publications and source records attributed to C Wells.

At least 37 records · Page 2Linked to original sources
PubMed2002

Is radiotherapy needed after breast conservation for small invasive breast cancers?

AIMS: The purpose of this study was to determine the rate of local recurrence in patients with small invasive breast cancers (<1 cm) who had been treated with breast-conserving surgery either with (group 1) or without (group 2) adjuvant radiotherapy. METHODS: This is a retrospective study of 110 patients with an invasive breast cancer less than 1 cm in size, treated in our centre by breast-conserving surgery. Parameters examined included age at and mode of presentation, histopathological features, adjuvant therapy, length of follow-up and outcome in terms of local recurrence rate and death. RESULTS: In group 1 there were 59 women of median age 57 (38-80) years. The median tumour size was 9 (1-10) mm and median follow-up was 74 (15-110) months. There were no local recurrences. In group 2 the median age at presentation was 59 (48-81) years. The median tumour size was 7 (2-10) mm and median follow-up was 47 (14-93) months. There were three non-breast-cancer related deaths and three local recurrences (6%). CONCLUSIONS: A local recurrence rate of 6% at almost 4 years median follow-up suggests that it may be possible to avoid adjuvant radiotherapy in a subgroup of largely screen-detected, node-negative patients with invasive tumours less than 1 cm, in whom adequate local excision is performed. Further follow-up is required to substantiate this.

Adult↗
PubMed2002

Induction of Nramp2 in activated mouse macrophages is dissociated from regulation of the Nramp1, classical inflammatory genes, and genes involved in iron metabolism.

Nramp2 is a widely expressed metal-ion transporter that is involved in dietary iron absorption in the duodenum and iron uptake from transferrin in peripheral tissues. Nramp1 is a related gene involved in regulation of host pathogen interaction. Nramp2 has at least two alternatively spliced isoforms, one of which contains an iron-responsive element in its 3'-untranslated region. In this study, we investigated the regulation of both isoforms of Nramp2 in activated primary macrophages from mouse strains with wild-type (Bcg(r)) or mutant (Bcg(s)) alleles. The Nramp2-IRE and/or -nonIRE transcripts were up-regulated in all mouse strains analyzed after treatment with interferon-gamma and lipopolysaccharide. cDNA microarray analysis revealed that Nramp2 regulation is controlled discordantly from other iron-regulated genes and classical macrophage-activation genes in different mouse strains. We suggest that Nramp2 is regulated independently of known iron-responsive genes in macrophages, and its function in host defense is unrelated to Nramp1.

Animals↗
PubMed2002

Anti-tuberculosis drug resistance in community and prison patients, Orel Oblast, Russian Federation.

SETTING: Orel Oblast, Russian Federation. OBJECTIVES: To determine baseline levels of anti-tuberculosis drug resistance in Orel Oblast. DESIGN: Drug susceptibility testing (DST) records from 1 July 1999 to 30 June 2000 for patients with sputum acid-fast bacilli smear-positive pulmonary tuberculosis were reviewed. Treatment and incarceration status were obtained from the tuberculosis register. Patients with 1 month or less of prior treatment were defined as new cases; those previously treated for more than 1 month were defined as retreatment cases. RESULTS: Of 246 smear-positive isolates, 212 (86%) had DST performed. Of these, 190 (90%) were from new and 22 (10%) from retreatment cases; 171 (81%) were from community and 41 (19%) were from prison patients. Any drug resistance was more common among prison than community patients (44% vs. 30%, P = 0.05). MDR-TB was found in 14 (6.6%) of 212 isolates, and was more prevalent in prison compared with community patients (12% vs. 5%, P = 0.05). Retreatment cases were more likely than new cases to have MDR-TB (prevalence ratio [PR] = 8.5, 95%CI = 3.3-22.3), although the PR was higher for prison than for community retreatment cases (10.0 vs. 5.8). CONCLUSIONS: New cases with MDR-TB were less prevalent in Orel Oblast compared with other survey sites in Russia. Any drug resistance and MDR-TB were associated with prior treatment, especially in the prison population. Continued monitoring of trends in drug resistance following DOTS implementation is needed.

Adult↗
PubMed2001

Molecular structure and conformation of cyclopropylbenzene as determined by ab initio molecular orbital calculations, pulsed-jet fourier transform microwave spectroscopic, and gas-phase electron diffraction investigations.

Ab initio computational, microwave spectroscopic, and electron diffraction techniques have been used to study the gas-phase structure of cyclopropylbenzene. Theoretical calculations at the HF, B3LYP, and MP2 levels for basis sets 6-31G(d) and 6-311G(d) have been carried out. Both MP2 and B3LYP calculations showed the bisected form to be lower in energy (245/157 and 660/985 cal mol(-1), respectively, for basis sets 6-311G(d)/6-31G(d)). Rotational constants for the bisected form of the parent and eight singly substituted (13)C isotopic species were obtained. The selection rules of the observed rotational transitions and the facts that eight (rather than six) singly substituted (13)C isotopers are observed and assigned and that seven of the compound's nine carbon atoms lie in the molecule's symmetry plane required the molecule to exist in the bisected conformation. No transition from the perpendicular form was observed in the pulsed-jet microwave experiment. Gas-phase electron diffraction data were collected at a nozzle-tip temperature of 265 K. Least squares analyses were carried out using ED data alone and with the inclusion of microwave rotational constants. The principal structural results (r(g) and angle(alpha)) obtained from the combined ED/MW least-squares analysis are r(C-H)(av) = 1.093(6) A, r(C(7)-C(8))(v) = 1.514(20) A, r(C(8)-C(9))(d) = 1.507(26) A, r(C(7)-C(1)) = 1.520(25) A, r(C-C)(Ph) = 1.395(1) A, angleC(1)C(7)C(8) = 119.6(17) degrees, angleC(2)C(1)C(7) = 122.5(25) degrees, angleC(1)C(2)C(3) = 120.9(35) degrees, angleHC(8)C(9) = 116.7(20) degrees, angleHCC(Ph) = 120.0 degrees (assumed).

Journal Article↗
PubMed2001

Predictors of positive margins after local excision of ductal carcinoma in situ.

BACKGROUND: This study aimed to examine the association between clinicopathologic parameters and positive margins in women with ductal carcinoma in situ (DCIS) treated by breast-conserving surgery (BCS). METHODS: We retrospectively reviewed the clinical, radiologic, and pathologic data of 100 women who had undergone BCS for DCIS in our center. RESULTS: Sixty-seven percent of patients presented via breast screening and 55% of all cases were diagnosed preoperatively on fine needle aspiration cytology ([FNAC] ie, C5). Overall, 45% of patients had clear margins after initial local excision. Positive margins showed a nonsignificant trend of association with distribution of microcalcifications (MCC), nonconsultant operating surgeon, inconclusive preoperative FNAC, presence of necrosis, and low specimen weight. There was a highly significant association between low grade DCIS (P = 0.003) and incomplete excision. There was no significant association with age, associated invasive focus, morphology of MCC, or with mode of presentation. CONCLUSION: Positive margins after local excision of DCIS are significantly associated with low nuclear grade, and preoperative determination of nuclear grade by core biopsy may have surgical implications.

Biopsy, Needle↗
PubMed2001

Does intraductal breast cancer spread in a segmental distribution? An analysis of residual tumour burden following segmental mastectomy using tumour bed biopsies.

INTRODUCTION: Breast-conserving surgery for early breast cancer is now routinely used as an alternative to mastectomy. Despite post-operative radiotherapy, early local recurrence of tumour remains a concern. It has been reported that invasive and in-situ ductal carcinoma spread locally through the ductal tree in a segmental distribution, however, there is no consensus as to the best surgical method to maximize tumour clearance whilst leaving a good cosmetic result. AIM: We aimed to measure the effectiveness of segmental mastectomy (excision of tumour plus associated segmental ductal tissue) in the clearance of different tumour types. Bed biopsy of the excision cavity was employed to assess the rate of incomplete excision or the multifocality of certain breast cancers. METHODS: One hundred and one patients with breast cancers underwent segmental mastectomy and cavity bed biopsies. Specimens were assessed for tumour type and completeness of excision. An excision of the cancer was considered incomplete if the margins were involved or if any of the bed biopsies showed residual or multifocal tumour. RESULTS: A total of 24 patients had incomplete tumour excision. Invasive ductal carcinoma was more likely to be completely excised by segmental mastectomy than invasive lobular carcinoma (P<0.05). Incomplete excision was associated with multifocality and the presence of extensive DCIS. The report of clear pathological margins was significantly more likely to be accurate, as measured by negative bed biopsies, in invasive ductal carcinoma when compared to invasive lobular carcinoma (P<0.05). CONCLUSION: These results support the concept that ductal carcinomas spread locally in a segmental fashion. Patients with invasive ductal carcinomas are more likely to benefit from breast conserving surgery that is tailored to include the associated ductal tissue, in a segmental fashioned excision.

Adult↗
PubMed2001

The potential effect of controlled ovarian hyperstimulation on follicular vascular perfusion: a study applying power Doppler ultrasonography within a treatment programme using donor sperm.

This was a prospective observational study to evaluate the effect of controlled ovarian hyperstimulation on follicular vascularity. A subjective grading system was applied to assess vascularity using transvaginal power Doppler ultrasonography on the day of insemination (32-36 hours post-HCG administration) in donor treatment cycles undergoing either controlled ovarian hyperstimulation (COH group) with gonadotrophin and intrauterine insemination or intracervical insemination with/without clomiphene stimulation (non-COH group). The incidence of follicles (81% vs. 53%; P < 0.05) as well as cycles (63% vs. 49%; P < 0.05) with uniformly high grade vascularity was significantly higher in treatments that had controlled ovarian hyperstimulation compared with unstimulated or clomiphene induced donor cycles. Pregnancy rates were higher and early pregnancy loss rates lower, in cycles with uniformly high grade follicular vascularity in both treatment groups compared with other vascularity grades. Using multiple logistic regression analysis, the only independent variable that was significantly related to pregnancy rates in this treatment programme was follicular vascularity. Controlled ovarian hyperstimulation appears to have an effect on follicular vascularity and this may contribute to improved outcome in donor insemination treatment programmes.

Journal Article↗
PubMed2001

Inhibition of isoniazid-induced expression of Mycobacterium tuberculosis antigen 85 in sputum: potential surrogate marker in tuberculosis chemotherapy trials.

Mycobacterium tuberculosis antigen 85 is induced in vitro by isoniazid (INH); its sustained induction in sputum during tuberculosis (TB) therapy predicts relapse. In this trial, rifampin or rifalazil inhibited the induction of sputum antigen 85 by INH in a dose-dependent fashion. This approach may facilitate the evaluation of new TB drugs.

Acyltransferases↗
PubMed2001

Safety and bactericidal activity of rifalazil in patients with pulmonary tuberculosis.

Rifalazil, also known as KRM-1648 or benzoxazinorifamycin, is a new semisynthetic rifamycin with a long half-life of approximately 60 h. Rifalazil has potent bactericidal activity against Mycobacterium tuberculosis in vitro and in animal models of tuberculosis (TB). Prior studies in healthy volunteers showed that once-weekly doses of 25 to 50 mg of rifalazil were well tolerated. In this randomized, open-label, active-controlled phase II clinical trial, 65 subjects with sputum smear-positive pulmonary TB received one of the following regimens for the first 2 weeks of therapy: 16 subjects received isoniazid (INH) (5 mg/kg of body weight) daily; 16 received INH (5 mg/kg) and rifampin (10 mg/kg) daily; 17 received INH (5 mg/kg) daily plus 10 mg of rifalazil once weekly; and 16 received INH (5 mg/kg) daily and 25 mg of rifalazil once weekly. All subjects were then put on 6 months of standard TB therapy. Pretreatment and day 15 sputum CFU of M. tuberculosis were measured to assess the bactericidal activity of each regimen. The number of drug-related adverse experiences was low and not significantly different among treatment arms. A transient decrease in absolute neutrophil count to less than 2,000 cells/mm(3) was detected in 10 to 20% of patients in the rifalazil- and rifampin-containing treatment arms without clinical consequences. Decreases in CFU counts were comparable among the four treatment arms; however, the CFU results were statistically inconclusive due to the variability in the control arms. Acquired drug resistance did not occur in any patient. Studies focused on determining a maximum tolerated dose will help elucidate the full anti-TB effect of rifalazil.

Adolescent↗
PubMed2001

An experimental inter-expert telepathology network using static imaging.

AIMS: To set up a network for remote consultation using static imaging telepathology via Internet connection between pathologists in different European countries, and to collect some numerical and subjective impressions on the usefulness of this form of telepathology. METHODS: A static image remote consultation network between 11 pathologists in nine European countries was set up; all pathologists were equipped with the same telepathology system. The pathologists formed three subject oriented subgroups concerned with prostate, melanoma, and soft tissue sarcoma pathology. Each pathologist sent and received a small number of cases, and data on each case were collected and analysed. The whole experiment was controlled through a World Wide Web site. RESULTS: A total of 56 case consultations on 34 different cases were exchanged. The average case document contained seven images, and contained 1.97 Mbytes of data. For cases in which data were recorded, average case preparation and remote consultation time was 55 minutes and 9.2 minutes, respectively. Transmission times averaged 3.9 minutes. In subjective impressions, reservations were expressed in several cases regarding the confidence that could be given to the diagnosis from the images presented. CONCLUSIONS: Remote consultation by telepathology via the Internet is now technically feasible and reasonably user friendly, but is only suitable as a method of disease diagnosis in some cases.

Diagnostic Imaging↗
PubMed2001

Specific changes to the mechanism of cell locomotion induced by overexpression of beta-actin.

Overexpression of beta-actin is known to alter cell morphology, though its effect on cell motility has not been documented previously. Here we show that overexpressing beta-actin in myoblasts has striking effects on motility, increasing cell speed to almost double that of control cells. This occurs by increasing the areas of protrusion and retraction and is accompanied by raised levels of beta-actin in the newly protruded regions. These regions of the cell margin, however, show decreased levels of polymerised actin, indicating that protrusion can outpace the rate of actin polymerisation in these cells. Moreover, the expression of beta*-actin (a G244D mutant, which shows defective polymerisation in vitro) is equally effective at increasing speed and protrusion. Concomitant changes in actin binding proteins show no evidence of a consistent mechanism for increasing the rate of actin polymerisation in these actin overexpressing cells. The increase in motility is confined to poorly spread cells in both cases and the excess motility can be abolished by blocking myosin function with butanedione monoxime (BDM). Our observations on normal myoblasts are consistent with the view that they protrude by the assembly and cross linking of actin filaments. In contrast, the additional motility shown by cells overexpressing beta-actin appears not to result from an increase in the rate of actin polymerisation but to depend on myosin function. This suggests that the additional protrusion arises from a different mechanism. We discuss the possibility that it is related to retraction-induced protrusion in fibroblasts. In this phenomenon, a wave of increased protrusion follows a sudden collapse in cell spreading. This view could explain why it is only the additional motility that depends on spreading, and has implications for understanding the differences in locomotion that distinguish tissue cells from highly invasive cell types such as leucocytes and malignant cells.

Actin Depolymerizing Factors↗
PubMed2000

Sexually dimorphic expression of protease nexin-1 and vanin-1 in the developing mouse gonad prior to overt differentiation suggests a role in mammalian sexual development.

The mammalian sex-determining pathway is controlled by the presence or absence of SRY expression in the embryonic gonad. Expression of SRY in males is believed to initiate a pathway of gene expression resulting in testis development. In the absence of SRY, ovary development ensues. Several genes have now been placed in this pathway but our understanding of it is far from complete and several functional classes of protein appear to be absent. Sex-determining genes frequently exhibit sexually dimorphic patterns of expression in the developing gonad both before and after overt differentiation of the testis or ovary. In order to identify additional sex-determining or gonadal differentiation genes we have examined gene expression in the developing gonads of the mouse using cDNA microarrays constructed from a normalized urogenital ridge library. We screened for genes exhibiting sexually dimorphic patterns of expression in the gonad at 12.5 and 13.5 days post-coitum, after overt gonad differentiation, by comparing complex cDNA probes derived from male and female gonadal tissue at these stages on micro-arrays. Using in situ hybridization analysis we show here that two genes identified by this screen, protease nexin-1 (Pn-1) and vanin-1 (Vnn1), exhibit male-specific expression prior to overt gonadal differentiation and are detected in the somatic portion of the developing gonad, suggesting a possible direct link to the testis-determining pathway for both genes.

Amidohydrolases↗
PubMed2000

Mice lacking the vascular endothelial growth factor-B gene (Vegfb) have smaller hearts, dysfunctional coronary vasculature, and impaired recovery from cardiac ischemia.

Vascular endothelial growth factor-B (VEGF-B) is closely related to VEGF-A, an effector of blood vessel growth during development and disease and a strong candidate for angiogenic therapies. To further study the in vivo function of VEGF-B, we have generated Vegfb knockout mice (Vegfb(-/-)). Unlike Vegfa knockout mice, which die during embryogenesis, Vegfb(-/-) mice are healthy and fertile. Despite appearing overtly normal, Vegfb(-/-) hearts are reduced in size and display vascular dysfunction after coronary occlusion and impaired recovery from experimentally induced myocardial ischemia. These findings reveal a role for VEGF-B in the development or function of coronary vasculature and suggest potential clinical use in therapeutic angiogenesis.

Aging↗
PubMed2000

Genomics meets genetics: towards a mutant map of the mouse.

Phenotype-driven mutagenesis approaches in the mouse will deliver a vastly expanded mouse mutant resource and can be expected to lead to the identification of novel genes and pathways, enabling the emergence of new insights into mammalian gene function. In order for this goal to be realized, developments in genomics need to be harnessed to progress in mouse mutagenesis. We need firstly to generate a mutant map of the mouse, devising and employing rapid methods for the genetic mapping of the growing mouse mutant resource. Secondly, we need to be able to rapidly identify and assess candidate genes in the vicinity of the mapped mutations. Developments in mapping and genotyping technology are described that will potentially speed the construction of a rich mutant map of the mouse. In addition, the benefits of comparative sequencing of the human and mouse genomes are reviewed. The availability of both human and mouse genome sequences will underpin the evolution of a comprehensive and well annotated mammalian gene map that will significantly enhance our ability to move rapidly from mapped mutation to the identification of the underlying gene.

Animals↗
PubMed2000

Implementation of a large-scale ENU mutagenesis program: towards increasing the mouse mutant resource.

Systematic approaches to mouse mutagenesis will be vital for future studies of gene function. We have begun a major ENU mutagenesis program incorporating a large genome-wide screen for dominant mutations. Progeny of ENU-mutagenized mice are screened for visible defects at birth and weaning, and at 5 weeks of age by using a systematic and semi-quantitative screening protocol-SHIRPA. Following this, mice are screened for abnormal locomotor activity and for deficits in prepulse inhibition of the acoustic startle response. Moreover, in the primary screen, blood is collected from mice and subjected to a comprehensive clinical biochemical analysis. Subsequently, secondary and tertiary screens of increasing complexity can be used on animals demonstrating deficits in the primary screen. Frozen sperm is archived from all the male mice passing through the screen. In addition, tail tips are stored for DNA. Overall, the program will provide an extensive new resource of mutant and phenotype data to the mouse and human genetics communities at large. The challenge now is to employ the expanding mouse mutant resource to improve the mutant map of the mouse. An improved mutant map of the mouse will be an important asset in exploiting the growing gene map of the mouse and assisting with the identification of genes underlying novel mutations-with consequent benefits for the analysis of gene function and the identification of novel pathways.

Animals↗
PubMed2000

A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse.

As the human genome project approaches completion, the challenge for mammalian geneticists is to develop approaches for the systematic determination of mammalian gene function. Mouse mutagenesis will be a key element of studies of gene function. Phenotype-driven approaches using the chemical mutagen ethylnitrosourea (ENU) represent a potentially efficient route for the generation of large numbers of mutant mice that can be screened for novel phenotypes. The advantage of this approach is that, in assessing gene function, no a priori assumptions are made about the genes involved in any pathway. Phenotype-driven mutagenesis is thus an effective method for the identification of novel genes and pathways. We have undertaken a genome-wide, phenotype-driven screen for dominant mutations in the mouse. We generated and screened over 26,000 mice, and recovered some 500 new mouse mutants. Our work, along with the programme reported in the accompanying paper, has led to a substantial increase in the mouse mutant resource and represents a first step towards systematic studies of gene function in mammalian genetics.

Animals↗