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Biomedical subjects

J Berry

Publications and source records attributed to J Berry.

At least 55 records · Page 3Linked to original sources
PubMed1997

A phase II trial of circadian-timed paclitaxel and cisplatin therapy in metastatic breast cancer.

PURPOSE: In a phase II study with combination paclitaxel and cisplatin in metastatic breast cancer using circadian timing, we attempted to maximise response and minimise toxicity. MATERIALS AND METHODS: Forty-one patients with histologically-proven metastatic breast cancer with or without previous chemotherapy were treated with Paclitaxel 135 mg/m2 administered as a three-hour infusion at 06.00 hours followed by cisplatin 75 mg/m2 as a one-hour infusion at 18.00 hours utilising circadian timing. Six cycles were planned once every 21 days. Response assessment was performed every two cycles, and toxicity was measured using WHO criteria. RESULTS: All patients were evaluable for response and toxicity. There were nine (22%) complete responses (CR), and 24 (59%) partial responses (PR), for an overall response rate of 80% (95% confidence interval (CI) 69-92). Responses were seen in patients previously treated with anthracyclines (75%) (95% CI 57-92), and in patients who had had no prior chemotherapy (90%) (95% CI 71-100). Responses were seen in all metastatic sites: liver 80%, lung 76%, bone 69%, and soft tissues 71%. The overall median response duration was seven months (range 3-26, 95% CI 5.0-9.8), and 14 of the responses (42%), (95% CI 28-62) were durable. A total of 212 cycles of chemotherapy were given. There were 15 episodes (7%) of grade 3-4 neutropenia, seven (3.2%) of grade 3-4 neurologic toxicity, and three (1.4%) of grade 3-4 nephrotoxicity. There were no toxic deaths. CONCLUSION: The combination of paclitaxel and cisplatin is very effective in metastatic breast cancer, and with application of circadian timing, toxicity has been acceptable. This combination is being tested as primary therapy in locally-advanced breast cancer at our institution.

Adult↗
PubMed1997

DNA vaccination with the major outer-membrane protein gene induces acquired immunity to Chlamydia trachomatis (mouse pneumonitis) infection.

The efficacy of DNA vaccination for prevention of Chlamydia trachomatis infection was studied using the murine model of pneumonia induced by the mouse pneumonitis (MoPn) isolate of C. trachomatis. Intramuscular DNA immunization with two chlamydial genes, one that encodes the major outer-membrane protein (MOMP) and one that encodes a cytoplasmic enzyme (cytosine triphosphate [CTP] synthetase) were tested. The MOMP DNA vaccine but not the CTP synthetase DNA vaccine generated significant delayed-type hypersensitivity and serum antibodies to MoPn elementary bodies and reduced the peak growth of MoPn by >100-fold following lung challenge infection. MOMP DNA immunization suggests a new approach to vaccine development for prevention of human chlamydial infection.

Animals↗
PubMed1997

A prospective study of VEC-POB and POCE chemotherapy in aggressive non-Hodgkin's lymphoma.

The optimal combination and scheduling of chemotherapy for aggressive non-Hodgkin's lymphoma is unclear, and the elderly have a poor tolerance to treatment. A Phase II prospective study was undertaken using outpatient weekly combination chemotherapy: the VEC-POB (etoposide, epirubicin, cyclophosphamide, cisplatin, Oncovin, bleomycin, and prednisone) regimen in patients < 60 years and less intensive POCE (etoposide, Oncovin, cyclophosphamide, and epirubicin) in patients > or = 60 years. All patients with intermediate and high-grade lymphoma (International Working Formulation) with bulky disease and/or advanced stages (III, IV) seen between January 1991 and June 1992 were entered. Of 29 patients treated with VEC-POB, 23 patients (79%) achieved complete remission (CR), with one (3%) toxic death. Overall survival at 29 months is 67%, and disease-free survival at 60 months is 60%. Of 29 patients treated with POCE, 14 achieved CR, with three (10%) toxic deaths. Overall survival is 58% at 18 months, and disease-free survival at 10 months is 50%. Adverse prognostic factors were analyzed. The results are comparable to the best results achieved with other regimens, and toxicity is acceptable.

Adult↗
PubMed1997

Effect of tamoxifen on the pharmacokinetics of doxorubicin in patients with non-Hodgkin's lymphoma.

The authors examined the effect of tamoxifen (TAM), a multiple-drug resistance modulator, on the pharmacokinetics of doxorubicin (DOX) in patients with non-Hodgkin's lymphoma treated according to the CHOP-protocol which included DOX, cyclophosphamide, vincristine, and prednisone. The dose of DOX was 50 mg/m2, but was reduced 25% if the patient was older than 60 years. Of these, 10 randomly-selected patients received a daily dose of 480 mg of TAM (Group-1) and 10 others did not (Group-2). Blood samples were collected at different time intervals, and DOX was measured in plasma by liquid chromatography. The concentration-time data of DOX exhibited the characteristics of the two-compartment open model well. The mean (SEM) values of alpha, beta, k12, k21, k10, Vc, Vss, AUC, total clearance, and mean residence time observed in Group-1 were 4.06 (0.96) hr(-1), 0.0395 (0.0068) hr(-1), 3.13 (0.79) hr(-1), 0.264 (0.052) hr(-1), 0.708 (0.19) hr(-1), 525 (156) l/m2, 1060 (163) l/m2, 1145 (234) microg x hr/l, 49.3 (8.5) l/hr x m2, and 26.8 (6.6) hours, respectively. Those in Group-2 were 4.99 (1.13) hr(-1), 0.0432 (0.0073) hr(-1), 2.46 (0.63) hr(-1), 0.111 (0.026) hr(-1), 2.46 (0.86) hr(-1), 231 (53) l/m2, 812 (149) l/m2, 1690 (276) microg x hr/l, 30.3 (4.1) l/hr x m2, and 29.7 (5.1) hours, respectively. Of these parameters, the difference between the two groups was significant (p < or = 0.0169) only in k21. Thus, the coadministration of TAM at the earlier-mentioned dose appears generally to have no significant influence on the pharmacokinetics of doxorubicin when used in the CHOP-protocol.

Adult↗
PubMed1997

Local Research Ethics Committees can audit ethical standards in research.

OBJECTIVES: To show that a Local Research Ethics Committee (LREC) can carry out an audit of ethical standards in research. To find out if a researcher met certain ethical standards in recruiting subjects for clinical trials and in obtaining their consent. DESIGN: Postal questionnaire. SETTING: Clinical research by one doctor during one year. SUBJECTS: Eleven patients entered in clinical trials. MAIN OUTCOME MEASURES: Success in ethics committee obtaining data. Achievement of ethical standards in recruitment of subjects and in obtaining consent. RESULTS: The audit was successfully carried out and standards were partly met. CONCLUSIONS: Local Research Ethics Committees can carry out audits of the conduct of research projects which they have approved. Provision for possible audits can be made at the time of application to the committee. Our committee thought the ethical standards in the research which we audited were acceptable.

Comprehension↗
PubMed1997

Hormonal factors and the laboratory detection of Chlamydia trachomatis in women: implications for screening?

One thousand and fifty-six new and re-registered consecutive women attending a genitourinary medicine clinic requiring speculum examination were screened for Chlamydia trachomatis by enzyme immunoassay (IDEIA, Dako Diagnostics Ltd). Of 1022 women who had results available for both cervix and urethra C. trachomatis was detected in 8.8% (89/1022) in any site, 2.3% (23/1022) in both sites, 4.9% (51/1022) at the cervix alone and 1.5% (15/1022) at the urethra alone. Thus sampling at the urethra increased detection by 17% (15/89). Analysis of 808 women with a regular menstrual cycle showed a significant association of combined oral contraceptive use, age and ectropion with the detection of C. trachomatis. The detection of C. trachomatis showed a significant variation with the menstrual cycle (P = 0.023) (relative risk (rr) 1.7 (95% confidence intervals (CI) 1.0-2.8)). It was detected significantly more often in the latter part. Stepwise logistic regression analysis revealed that ectropion and age were the stronger determinants of C. trachomatis detection and not oral contraceptive use or menstrual cycle. The variation in detection of C. trachomatis with the menstrual cycle was independently associated with combined oral contraceptive use and the lack of a cervical ectropion. The increased detection at the cervix was present after the second week in combined oral contraceptive users (P = 0.008) (rr = 2.3 (1.2-4.5)) but only after the 3rd week in women without an ectropion (P = 0.004) (rr = 2.7 (1.3-5.5)). Combined oral contraceptives, ectropion and youth, are markers for the carriage of C. trachomatis in the lower genital tract of women. It is also detected significantly more often in the latter part of the menstrual cycle in women who are oral contraceptive users.

Adolescent↗
PubMed1996

Environment of infants during sleep and risk of the sudden infant death syndrome: results of 1993-5 case-control study for confidential inquiry into stillbirths and deaths in infancy. Confidential Enquiry into Stillbirths and Deaths Regional Coordinators and Researchers.

OBJECTIVE: To investigate the role of sleeping arrangements as risk factors for the sudden infant death syndrome after a national risk reduction campaign. DESIGN: Two year population based case-control study. Parental interviews were conducted for each infant who died and for four controls matched for age and date of interview. SETTING: Three regions in England with a total population of 17 million people. SUBJECTS: 195 babies who died and 780 matched controls. RESULTS: Prone and side sleeping positions both carried increased risks of death compared with supine when adjusted for maternal age, parity, gestation, birth weight, exposure to smoke, and other relevant factors in the sleeping environment (multivariate odds ratio = 9.00 (95% confidence interval 2.84 to 28.47) and 1.84 (1.02 to 3.31), respectively). The higher incidence of side rather than prone sleeping led to a higher population attributable risk (side 18.4%, prone 14.2%). More of the infants who died were found with bed covers over their heads (21.58; 6.21 to 74.99). The use of a dummy had an apparent protective effect (0.38; 0.21 to 0.70). Bed sharing for the whole night was a significant risk factor for infants whose mothers smoked (9.25; 2.31 to 34.02). No protective effect of breast feeding could be identified on multivariate analysis. CONCLUSIONS: This study confirms the importance of certain risk factors for the sudden infant death syndrome and identifies others-for example, covers over the head, side sleeping position-which may be amenable to change by educating and informing parents and health care professionals.

Bedding and Linens↗
PubMed1996

Smoking and the sudden infant death syndrome: results from 1993-5 case-control study for confidential inquiry into stillbirths and deaths in infancy. Confidential Enquiry into Stillbirths and Deaths Regional Coordinators and Researchers.

OBJECTIVE: To investigate the effects of exposure to tobacco smoke and of parental consumption of alcohol and illegal drugs as risk factors for the sudden infant death syndrome after a national risk reduction campaign which included advice on prenatal and postnatal avoidance of tobacco smoke. DESIGN: Two year population based case-control study. Parental interviews were conducted for each infant who died and four controls matched for age and date of interview. SETTING: Three regions in England with a total population of 17 million people. SUBJECTS: 195 babies who died and 780 matched controls. RESULTS: More index than control mothers (62.6% v 25.1%) smoked during pregnancy (multivariate odds ratio = 2.10; 95% confidence interval 1.24 to 3.54). Paternal smoking had an additional independent effect when other factors were controlled for (2.50; 1.48 to 4.22). The risk of death rose with increasing postnatal exposure to tobacco smoke, which had an additive effect among those also exposed to maternal smoking during pregnancy (2.93; 1.56 to 5.48). The population attributable risk was over 61%, which implies that the numbers of deaths from the syndrome could be reduced by almost two third if parents did not smoke. Alcohol use was higher among index than control mothers but was strongly correlated with smoking and on multivariate analysis was not found to have any additional independent effect. Illegal drug use was more common among the index parents, and paternal use of illegal drugs remained significant in the multivariate model (4.68; 1.56 to 14.05). CONCLUSIONS: This study confirms the increased risk of the sudden infant death syndrome associated with maternal smoking during pregnancy and shows evidence that household exposure to tobacco smoke has an independent additive effect. Parental drug misuse has an additional small but significant effect.

Alcohol Drinking↗
PubMed1996

Impact of pregnancy on non-metastatic breast cancer: a case control study.

The diagnosis of breast cancer during pregnancy remains uncommon and therefore leads to non-standardized management. We reviewed retrospectively 28 such women treated at this centre and compared them with age and stage matched controls. Differences in management and outcome were analysed for statistical significance. There was no significant difference in overall survival (P = 0.86) and relapse-free survival (P = 0.48) between the two groups. Chemotherapy after the first trimester of pregnancy carried no significant morbidity. Pregnancy does not appear to be an adverse prognostic factor for breast cancer.

Adult↗
PubMed1995

Localization and expression of osteopontin in mineralized and nonmineralized tissues of the periodontium.

To summarize results from various studies focusing on determining the expression/localization of BSP and OPN during tooth root development, there is general agreement that OPN is expressed/localized to the root surface during cementogenesis and is also seen throughout the PDL region. The expression/localization of OPN to odontoblasts and its role in dentinogenesis is less apparent. Recent studies directed at establishing odontoblast cell lines should help to resolve this conflict. Studies on BSP expression during tooth root formation indicate a very precise expression and localization of this molecule during cementogenesis indicating that this molecule may play an important role in the formation of this mineralized tissue. However, as with OPN, the expression of BSP and its role in dentin formation is not clearly defined.

Animals↗
PubMed1995

Changes of mitochondrial mass in the hemopoietic stem cell line FDCP-mix after treatment with etoposide: a correlative study by multiparameter flow cytometry and confocal and electron microscopy.

FDCP-Mix, a pluripotent murine hemopoietic stem cell line which undergoes typical internucleosomal cleavage of DNA when induced to apoptosis by either drugs or withdrawal of growth factor (interleukin-3) was studied after treatment with the topoisomerase II inhibitor etoposide (0.5-4 microM). An increase in autolytic activity was the major early morphological change within the cytoplasm, with mitochondria as the main target for autolytic digestion. Despite this macroautophagy, thin sections showed a high number of mitochondria, suggesting mitochondrial proliferation as a result of drug treatment. This observation of an increase in the number of mitochondria was confirmed by flow cytometric studies of mitochondrial overall mass. Multiparameter flow cytometry of cells double stained with propidium iodide and nonyl-acridine orange gave an accurate assay for mitochondrial mass in relation to cell cycle stages. The increase in mitochondrial mass was found in all cell cycle stages. The results suggest a drug-induced proliferation of mitochondria separate from the processes involved in the doubling of mitochondrial mass during the cell cycle and a decline of mitochondria in the later stages of apoptosis.

Acridine Orange↗
PubMed1995

A case of experiential hallucinations of unknown origins, or the mystery of the mime.

A case is described of repetitive familiar activities apparently accompanied by a hallucinated physical environment in an older brain-injured man with an amputation of the left temporal lobe. A parallel is drawn to the 'experiential hallucinations' described in psychomotor seizures and direct stimulation of the cortex.

Activities of Daily Living↗
PubMed1995

Role of two mineral-associated adhesion molecules, osteopontin and bone sialoprotein, during cementogenesis.

Adhesion molecules and their cell membrane receptors are known to play important regulatory roles in cell differentiation. Consequently, the following experiments were conducted to determine the role of two adhesion molecules, bone sialoprotein (BSP) and osteopontin (OPN) in tooth root formation. Developing murine molar tooth germs at sequential stages of development (developmental days 21-42) were analyzed using immunohistochemical and in situ hybridization techniques. While BSP was localized to alveolar bone and odontoblasts early in development, BSP was distinctly localized to the cemental root surface at latter periods coincident with the initiation of root formation and cementogenesis. Conversely, OPN was distributed in a nonspecific fashion throughout the PDL and the eruption pathway of the forming tooth. In situ hybridization confirmed that cells lining the root surface express BSP. The fact that BSP is specifically localized to the cemental surface suggests that this protein is involved in cementoblast differentiation and/or early mineralization of the cementum matrix. Localization of OPN to non-mineralized tissues further suggests that OPN functions as an inhibitor of mineralization during periodontal ligament formation. These findings collectively suggest that BSP and OPN are intimately involved in the sequence of cellular and molecular events accompanying cementogenesis.

Alveolar Process↗
PubMed1994

Mutations in Ig V(D)J genes are distributed asymmetrically and independently of the position of V(D)J.

To study the distribution of somatic mutations in the DNA flanking the 5' side of rearranged Ig V genes, the 5' region of 14 to 21 mutant forms of three different V(D)J were sequenced. These were compared with a fourth V(D)J for which the flanking sequences of 10 mutant forms are known. The leader intron of these four V genes varied from 82 to 365 nucleotides in length. Analysis of the data showed that: 1) The mutation frequency is distributed asymmetrically with respect to the V(D)J exon with skewing in the 3' direction. 2) The distribution of mutations 5' of V(D)J seems to be related to the size of the leader intron. The significance of these findings for models of hypermutation is discussed.

Animals↗
PubMed1994

Conformational mimicry of a chlamydial neutralization epitope on filamentous phage.

Conformational constraints were imposed on a peptide epitope from Chlamydia trachomatis to improve its ability to elicit antibodies that cross-react with native antigen. Appropriate constraints were discovered by a strategy that required no prior knowledge of the epitope's native conformation. First, we constructed a library of 3.2 x 10(5) peptides in which the epitope's contact residues were subject to random conformational constraints, each constrained peptide being fused genetically to the surface of a filamentous phage vector. Next, we selected phage displaying the most native-like peptides in the library by affinity purification with antibodies that bind the epitope only in its native conformation. Finally, we immunized mice with the selected phage and titered the resulting antisera against both whole cells and unconstrained peptide. The ratio of anti-cell titer to anti-peptide titer, which reflects the channeling of the antibody response to the native epitope, was up to five times higher for affinity-selected phage than for unselected peptide phage. In this case, therefore, "antigenic fitness," the ability of a peptide to bind antibodies specific for native epitope, correlated with "immunogenic fitness," its ability to elicit antibodies that are effective against the native antigen on an invading pathogen. If the correlation is general, surveying thousands or millions of peptides for antigenic fitness with phage display technology may be a simple but effective pre-screen for immunogenic fitness, which is costly to assess directly.

Amino Acid Sequence↗