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Biomedical subjects

R B Jones

Publications and source records attributed to R B Jones.

At least 127 records · Page 7Linked to original sources
PubMed1997

Changes in tonic immobility and the GABA-benzodiazepine system in response to handling in the chick.

Changes in the GABA-benzodiazepine system were investigated following regular handling of male chicks. Compared with handling-naive chicks, those exposed to 10 days of gentle handling required a larger number of inductions and had a lower duration of tonic immobility. Corresponding biochemical changes occurred, with handling-habituated chicks having a significantly lower basal [14C]GABA release from archistriatal slices and a reduction in the Bmax of [3H]muscimol binding in the forebrain. Benzodiazepine binding in the archistriatum was investigated using in vitro quantitative receptor autoradiography. Binding was localised in the anterior, mediale, dorsalis, and ventralis intermedium nuclei of the archistriatum, and there was significantly more binding in the anterior and ventralis intermedium/mediale archistriatum nuclei than in the dorsalis intermedium archistriatum nuclei. Benzodiazepine binding was not altered after handling in any of the investigated nuclei of the archistriatum. The results suggest that whereas several days of gentle handling in chicks leads to a decrease in forebrain GABAA receptors and a decrease in GABA release from the archistriatum, there are no accompanying changes in benzodiazepine receptors. Regular handling exerts a specific effect on chicks: it reduces their fear or human beings but not that of novel places or objects. It is possible that the pattern of biochemical changes observed in the present study may be specifically associated with this particular behavioural modification rather than with a change in general fearfulness.

Animals↗
PubMed1997

Evaluation of BTS 67 582, a novel antidiabetic agent, in normal and diabetic rats.

1. The effect of BTS 67 582, a novel antidiabetic agent, has been evaluated on plasma glucose and plasma insulin in normal and streptozotocin-induced diabetic rats. 2. BTS 67 582 (3 to 300 mg kg-1, p.o.) caused a dose- and time-dependent reduction in plasma glucose and an increase in plasma insulin in both fasted and glucose-loaded normal rats. The ED50 for the glucose lowering effect of BTS 67 582 in fasted rats was 37.6, 18.4 and 18.5 mg kg-1 at 1, 2 and 4 h after administration respectively. 3. In streptozotocin-induced (50 mg kg-1, i.v.) diabetic rats, BTS 67 582 (37-147 mg kg-1, p.o.) caused significant reductions of plasma glucose following a glucose load, whereas glibenclamide (100 mg kg-1, p.o.) was ineffective. BTS 67 582 significantly increased plasma insulin compared to controls whereas glibenclamide did not. 4. BTS 67 582 did not displace [3H]-glibenclamide from its binding sites in rat brain, guinea-pig ventricle or the HIT-T15 insulinoma beta-cell line. BTS 67 582 does not therefore appear to modulate its action via an effect on the 'sulphonylurea' receptor. 5. In fasted rats, the glucose lowering effect of BTS 67 582 (100 mg kg-1 p.o.) and glibenclamide (1 mg kg-1, p.o.) were antagonized by diazoxide (30 mg kg-1, i.p.). In addition BTS 67 582, like glibenclamide, caused a dose-dependent rightward shift of cromakalim-induced relaxation of noradrenaline precontracted rat aortic strips, suggesting the involvement of KATP channels. 6. In summary, BTS 67 582 produces a blood glucose-lowering effect in normal and streptozotocin-induced diabetic rats associated with increased insulin concentrations. This effect appears to be due to a blockade of ATP-sensitive potassium channel activity via a different binding site to that of glibenclamide.

Animals↗
PubMed1997

High-dose chemotherapy with autologous peripheral blood progenitor cell support for primary breast cancer in patients with 4-9 involved axillary lymph nodes.

Breast cancer patients with more than three involved axillary lymph have a high likelihood of relapse after adjuvant therapy. Early results of administration of high-dose chemotherapy (HDCT) and autologous peripheral blood progenitor cells (PBPC) to patients with primary breast cancer and > or = 10 involved axillary nodes have been encouraging. We performed a multicenter trial to determine whether HDCT could be safely administered to patients with primary breast cancer involving 4-9 axillary lymph nodes. Fifty-four patients with stage II or III breast cancer and 4-9 involved axillary lymph nodes received doxorubicin-based induction chemotherapy, followed by high-dose cyclophosphamide (5.625 g/m2), cisplatin (165 mg/m2), and BCNU (450 mg/m2) and PBPC mobilized by sargramostim (GM-CSF) or filgrastim (G-CSF). After completion of HDCT, patients received radiation therapy to the chest wall or involved breast, plus tamoxifen. Survival and disease-free survival, time to engraftment, and charges associated with HDCT were determined. Plasma concentrations of BCNU were determined and plasma AUC(BCNU) was calculated. Fifty-four patients were evaluable for survival and relapse-free survival. Fifty-two patients received HDCT with PBPC support and were evaluable for toxicity. Fifteen patients (29%) developed late pulmonary drug toxicity, which resolved with a 10-week course of corticosteroids in all but one affected patient, who subsequently died of pulmonary toxicity. Ten patients relapsed a median of 426 days (range 86-1117 days) after the start of induction chemotherapy, seven of whom have died. Forty-three patients are alive and breast cancer-free at a median of 947 days (range 661-1730 days) after the start of therapy, including one patient who developed myelodysplastic syndrome 809 days after the start of HDCT. Actuarial 4-year survival and disease-free survival from the start of treatment are 84 and 71%, respectively. Mean plasma AUC(BCNU) was 400 (range 82-1255) microgxmin/ml and was not statistically different from that measured in historical controls who received 600 mg/m2 of BCNU. Combined hospital and physician charges for patients treated at the University of Colorado decreased from a mean of $125845 for the first four patients to $77126 for the final seven patients. We conclude that HDCT with autologous PBPC can be administered with acceptable safety to patients with primary breast cancer involving 4-9 axillary lymph nodes. An ongoing, prospective randomized trial is evaluating the efficacy of HDCT for this patient group.

Adult↗
PubMed1997

Susceptibility of Chlamydia trachomatis to trovafloxacin.

Chlamydia trachomatis infections are a major cause of morbidity in the sexually active. While current therapy is usually effective, isolates demonstrating relative resistance to erythromycin or heterotypic resistance to erythromycin, tetracycline and their congeners have been described, establishing a need to continue to evaluate other antimicrobial agents for possible efficacy. In this study trovafloxacin, a compound related to the fluoroquinolones, was tested in tissue culture for in-vitro efficacy against 19 strains of C. trachomatis, including three strains known to exhibit heterotypic resistance. All strains were fully sensitive to trovafloxacin with a minimum inhibitory concentration at which 90% of inclusions were reduced (IR90) of 0.05 +/- 0.07 mg/L (mean +/- S.D.). The IR90 for the comparison antibiotics erythromycin, doxycycline and ofloxacin were 0.17 +/- 0.07, 0.10 +/- 0.03 and 0.35 +/- 0.15 mg/L respectively. Trovafloxacin is very active on a weight basis and deserves further evaluation.

Anti-Infective Agents↗
PubMed1997

Ease of capture in Japanese quail of two lines divergently selected for adrenocortical response to immobilization.

Divergent lines of Japanese quail have been genetically selected over several generations for a reduced (low stress, LS) or an exaggerated (high stress, HS) plasma corticosterone response to brief mechanical restraint. Female quail were housed in one mixed-line group (18LS + 18 HS) in one of the top-tier compartments of a brooder. At 32 d of age, the quail were removed individually by the experimenter, their identity and position in the order of capture were noted, and then they were placed in a separate compartment. Following brief respites, this procedure was repeated on 16 occasions. No differences were found between HS and LS quail in their ease of capture and no linear trends were apparent upon repeated testing of either strain. These findings have positive connotations for management and welfare because, although selection for a reduced adrenocortical stress response to restraint has apparently been accompanied by reduced fearfulness, it has not resulted in a potential and undesirable increase in the difficulty of capture and handling. Further, the significant tendencies found within and across lines for individual birds to be caught at similar stages of each trial has important implications for behavioral studies that involve putatively random sampling of a population.

Adrenal Cortex↗
PubMed1997

Psychogenic disorders of vision in childhood ("visual conversion reactions"): perspectives from adolescence: a research note.

Fifteen adolescents who had exhibited psychogenic disorders of vision in childhood were compared with a control group of adolescents who had experienced childhood visual dysfunction of organic origin. The principal modes of assessment were clinical interviews, the Parental Bonding Instrument (PBI), and self-report measures concerning specific personality traits. Adolescents who had previously presented with psychogenic disorder were more likely to (1) report having experienced school difficulties and the loss of a significant figure at the time of presentation, (2) rate their mothers as over-involved on the PBI and (3) report adjustment difficulties and obsessional personality traits in adolescence.

Adolescent↗
PubMed1997

Comparison of single-dose oral grepafloxacin with cefixime for treatment of uncomplicated gonorrhea in men. The STD Study Group.

In a randomized open study, 351 male patients with uncomplicated gonorrhea were given single oral doses of grepafloxacin (400 mg) or cefixime (400 mg). In the 299 microbiologically evaluable patients, urethral infections were cured in 99% (147 of 149) of those receiving grepafloxacin and 97% (145 of 150) of those given cefixime. Eradication rates for both regimens were 100% in the 16% (47 of 299) of participants who were infected with penicillin-resistant Neisseria gonorrhoeae and 97% in the 21% (62 of 299) of participants infected with tetracycline-resistant strains. Grepafloxacin is a well-tolerated alternative to cefixime for treatment of uncomplicated gonorrhea in males.

Administration, Oral↗
PubMed1997

Evaluation of the Vidas Chlamydia test to detect and verify Chlamydia trachomatis in urogenital specimens.

The Vidas Chlamydia test (CHL) is an automated enzyme-linked immunofluorescence assay for the detection of Chlamydia trachomatis. Positive and equivocal results are confirmed with a blocking assay. A mouse monoclonal antibody directed against the chlamydial lipopolysaccharides was used for the test. The CHL assay is widely used in Europe, but U.S. experience with it is limited. Three clinical test sites (The Arlington Hospital, Arlington, Va., Indiana University, Indianapolis, and the University of California, San Francisco) compared CHL with tissue culture (TC) for the identification of chlamydia in urogenital specimens (2,453 females and 850 males). True positives (TP) were defined as either TC positive or TC negative and CHL positive by a positive direct fluorescent-antibody assay or PCR test. Overall prevalence was 5.5% for females, 10.3% for male urethral swabs, and 10.7% for combined male TC urethral swabs and CHL with first catch urine (FCU) specimens. Compared to TP, CHL and TC had sensitivities of 89.6 and 94.1% with female cervical swabs and 90.9 and 86.4% with male urethral swabs, respectively. CHL sensitivity was 81.2 for male FCU specimens and 77.7% for matching male TC swabs. There were relatively few false-positive results, with all specificities being >99.4%. With the blocking assay, Vidas CHL specificity was >99.7%. However, male FCU specimen sensitivity was compromised because 9.2% (7 of 76) of the TP were initially positive but were not confirmed. An improvement in the Vidas blocking assay is needed before we can recommend its use with male urine. Alternatively, one could argue that the specificity of the test is so high that a confirmatory assay is not needed. For male and female swabs, the Vidas CHL assay has a performance that is similar to that of TC.

Bacteriological Techniques↗
PubMed1997

Peripheral blood stem cells for autografting.

High-dose therapy with autologous hematopoietic progenitor cell support is effective treatment for patients with a variety of high-risk malignancies. Accelerating of marrow recovery from near-lethal or lethal toxicity with hematopoietic cell support improves the safety and cost effectiveness of the high-dose regimens. Peripheral blood progenitor cells will soon replace marrow as the major source of hematopoietic support. This chapter reviews the techniques of peripheral blood progenitor cell collection, mobilization, purification (for tumor removal), and ex vivo expansion.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Histamine H2 receptor antagonist-refractory oesophagitis: the efficacy of long-term omeprazole maintenance treatment.

BACKGROUND: Erosive oesophagitis refractory to high dose histamine H2 receptor antagonists (definition: failure to heal fully after > or = 3 months' treatment with cimetidine 3.2 g or ranitidine 0.9 g) responds well to omeprazole 40 mg daily but frequently relapses when the patients are put back on maintenance H2 receptor antagonists at medium or even high dose (e.g. cimetidine 1.6 g and 3.2 g, respectively). AIM: To investigate the efficacy of maintenance omeprazole 20 mg daily in refractory erosive oesophagitis. PATIENTS & METHODS: In this open, sequential study, patients with H2 receptor antagonist-refractory oesophagitis were healed on omeprazole 40 mg daily and then put on maintenance H2 receptor antagonists (cimetidine 1.6 g or 3.2 g). Relapses were re-treated with omeprazole 40 mg; upon rehealing, patients were put on maintenance omeprazole 20 mg daily for up to 4.5 years. RESULTS: Healing on omeprazole occurred in 38 out of 39 patients (97%) at 12 weeks. Only six of the 38 patients (16%) relapsed (asymptomatic in half) during subsequent maintenance treatment, whereas all had relapsed earlier on high dose H2 receptor antagonists. CONCLUSION: Within the limits of interpretation of an open study, omeprazole 20 mg daily seems effective in maintaining prolonged remission in this group of patients with H2 receptor antagonist-refractory oesophagitis.

Adult↗
PubMed1996

Immunocytochemical detection of breast cancer cells in marrow and peripheral blood of patients undergoing high dose chemotherapy with autologous stem cell support.

Detection of small numbers of breast cancer cells is important in staging the disease and can be helpful in assessing the efficacy of purging regimens prior to autologous stem cell infusion. Immunohistochemical methods are potentially useful and broadly applicable for this purpose since they are simple to perform, sensitive, and may be quite specific. We have used a combination of four monoclonal antibodies [260F9, 520C9, 317G5 (Baxter Corp); BrE-3 (Dr. R. Ceriani)] against tumor cell surface glycoproteins in a sensitive immunocytochemical assay to identify breast tumor cells in bone marrow and peripheral blood. Immunostained cytospin preparations were fixed prior to staining to preserve cytological details of immunopositive cells. After immunostaining, slides were counterstained with hematoxylin to confirm the identify of labeled cells. In cytocentrifuge experiments in which small numbers of CAMA human breast tumor cells were added to bone marrow mononuclear cells, a linear relationship between the number of tumor cells added and the number of tumor cells detected was obtained over a broad range of tumor cell concentrations. The probability of detecting tumor cells was dependent on the number of cytocentrifuge slides examined. When ten slides (5 million cells) were examined, the probability of detecting tumor at a concentration of 4 tumor cells per million bone marrow mononuclear cells was 98%. In clinical specimens, tumor cells were detected in marrow aspirates from 73 of 240 (30%) patients undergoing autologous transplantation, including 70 (37%) of 190 patients with clinical stage IV disease, 0 of 7 patients with clinical stage III disease, and 3 of 43 (7%) patients with clinical stage II disease. Seventy-three of 657 peripheral blood specimens from 26 of 155 patients (17%) contained breast cancer cells with counts ranging from 1 to 97 tumor cells per million leukocytes. Tumor cells were most frequently found in the blood of patients with stage IV disease [21 of 107 (20%)] but were also found in a substantial number [5 of 44 (11%)] of patients with stage II disease. Positive selection of CD34-positive hematopoietic progenitor cells as well as negative purging methods such as incubation with 4-hydroxyperoxy-cyclophosphamide (4-HC) were evaluated with respect to tumor cell depletion. Selection of CD34-positive progenitor cells from bone marrow or peripheral blood resulted in log reduction of 1 to > 4 tumor cells reinfused at autologous transplantation. A lesser log reduction (up to 1) was demonstrated following 4-HC purging. We conclude that properly performed and controlled immunocytochemical staining of bone marrow and peripheral blood cytospins is a sensitive and simple way to detect and quantitate breast cancer cells in hematopoietic specimens harvested for autotransplantation and that CD34-positive progenitor cell selection results in significant reduction in the number of breast cancer cells reinfused with marrow or peripheral blood stem cells.

Antibodies, Monoclonal↗
PubMed1996

A phase I/II study of high-dose cyclophosphamide, cisplatin, and thioTEPA followed by autologous bone marrow and granulocyte colony-stimulating factor-primed peripheral-blood progenitor cells in patients with advanced malignancies.

The purpose of the present study was to determine the maximally tolerated dose of thioTEPA given with fixed high-dose cyclophosphamide (CPA) and cisplatin (cDDP) followed by autologous bone marrow (ABM) with or without granulocyte colony-stimulating factor (G-CSF)-primed peripheral-blood progenitor cells (PBPCs) in patients with advanced malignancies. Patients were required to have histologically documented malignancies and adequate renal, hepatic, pulmonary, and cardiac function. CPA was given at 1,875 mg/m2 per day as a 1-h i.v. infusion for 3 consecutive days, and cDDP was given at 55 mg/m2 per day as a 24-h continuous i.v infusion over 3 days concurrently with CPA. ThioTEPA was given once as a 1-h i.v. infusion (300-900 mg/m2) either following (the first 13 patients) or prior to CPA and cDDP. In all, 31 patients received PBPCs. A total of 46 patients were treated. There were 6 deaths among the 15 patients who did not receive PBPCs (13 received thioTEPA following CPA and cDDP). Among the other 31 patients who received PBPCs (all of whom also received thioTEPA prior to CPA and cDDP), there were 4 deaths, all involving patients with refractory ovarian carcinoma. The main toxicities were mucositis, esophagitis, hepatotoxicity, and nephrotoxicity. The median time required to achieve an absolute neutrophil count of 500 microliter was 10 days (range, 9-12 days) for those who received PBPCs and 15 days (range, 15-34 days) for those who did not receive PBPCs. Altogether, 47% of the major organ toxicities (grades 3 and 4 renal, hepatic, and cardiac toxicities) occurred among the 15 patients who did not receive PBPCs, although these patients received thioTEPA at the lowest 2 dose levels. There were 3 complete responses and 22 partial responses among 35 evaluable patients (overall response rate, 71%), with the median duration of response being 3.5 months (range, 2-17 months). The maximally tolerated dose of thioTEPA was 600 mg/m2 given as a 1-h i.v. infusion on the day prior to CPA and cDDP administration, The combination of high-dose CPA, cDDP, and thioTEPA is a well-tolerated regimen when thioTEPA is given prior to CPA and cDDP and when the combination also includes PBPCs in addition to ABM. This regimen is active in a variety of malignancies.

Adult↗
PubMed1996

Bone marrow metastases.

This article discusses the clinical significance of bone marrow metastases and the current methods being used to detect tumor cells in marrow. The strategies being investigated for eradicating cancer cells from marrow in patients receiving hematopoietic cell autografts also are reviewed.

Bone Marrow Neoplasms↗
PubMed1996

Renal function in high dose chemotherapy and autologous hematopoietic cell support treatment for breast cancer.

Autologous and allogeneic bone marrow grafting both require cytoreductive therapy but only the allogeneic procedure requires immunosuppressive agents. Allogeneic bone marrow transplantation has been reported to be associated with a high incidence of both renal failure and veno-occlusive disease (VOD) of the liver, the combination of which is associated with a high morbidity and mortality. There is less known about the frequency and severity of these complications in patients undergoing autologous bone marrow transplantation. In the present study renal, hepatic and other complications were examined in 232 patients with Stages II/III and IV breast cancer who were treated with high-dose chemotherapy and autologous hematopoietic cell support with either marrow or peripheral blood progenitor cells. The post-treatment severity of the renal dysfunction was classified as follows: Grade 0, normal renal function [< 25% decrement in glomerular filtration rate (GFR)]; Grade 1. mild renal dysfunction (> 25% decrement in GFR but < a twofold increase in serum creatinine); Grade 2, > twofold rise in serum creatinine but no need for dialysis; Grade 3 > than twofold rise in serum creatinine and need for dialysis. There were 102 patients (44%) who were classified as Grade 0 and 81 patients (35%) who were classified as Grade 1 renal dysfunction. Severe renal dysfunction (Grades 2 and 3) was observed in 49 of the 232 patients (21%). This severe renal dysfunction of 21% compares with a previously reported 53% incidence of severe renal dysfunction for allogeneic bone marrow transplantation. Similarly, the frequency of hepatic VOD was less (4.7% or 11 of 232 patients) in this autologous bone marrow transplant study as compared to a reported incidence of hepatic VOD ranging from 22 to 53% in large series of allogeneic bone marrow transplant patients. The severe renal dysfunction (Grades 2 and 3) in the present autologous hematopoietic cell support study correlated most significantly with sepsis, liver and pulmonary dysfunction. The major fall in GFR occurred during chemotherapy but before hematopoietic cell support, thus primarily incriminating the cytoreductive therapy rather than the hematopoietic cell support. The only significant effect of different chemotherapy protocols was, at four weeks, the Taxol-treated group had a significantly lower creatinine clearance as compared to the BCNU treated group.

Adult↗
PubMed1996

Vitamin C supplementation and fear-reduction in Japanese quail: short-term cumulative effects.

1. Fear-related behaviour was measured in individually-housed Japanese quail which had received either untreated drinking water (UDW) or a vitamin C solution (ascorbyl-2-polyphosphate, APP, 1 g L-ascorbic acid/1 for 1 or 4 d. Behavioural tests were carried out at 24 or 27 d of age. Water consumption was measured daily and plasma ascorbic acid (AA) content was assayed after differential treatment for 1 or 4 d. 2. The quail in the APP treatment groups drank significantly more than did those receiving untreated drinking water. 3. Supplementation with APP raised plasma AA concentrations substantially above those found in UDW quail. The lower AA concentrations found after APP treatment for 4 d rather than one may have reflected either inter-assay variation or limited intestinal absorption following excess ingestion. 4. Quail treated with APP showed less home-cage avoidance of a novel object and shorter tonic immobility fear reactions than did the UDW birds. The UDW quail showed remarkably similar avoidance and TI scores on test days 1 and 4. Conversely, continued treatment with APP further reduced avoidance scores but, although TI durations fell slightly with continued treatment there were no significant day effects. 5. It was concluded that APP supplementation can reduce underlying fearfulness but that it may not be necessary to continue treatment for longer than 24 h immediately prior to a known frightening event.

Analysis of Variance↗
PubMed1996

Threat-induced behavioural inhibition in Japanese quail genetically selected for contrasting adrenocortical response to mechanical restraint.

1. Behavioural and adrenocortical responses to brief mechanical restraint were examined in 28-d-old female Japanese quail of two lines which had been genetically selected over several generations for either reduced (LS, low stress) or exaggerated (HS, high stress) plasma corticosterone response to brief immobilisation in a metal box. 2. As expected, quail of the LS line showed lower adrenocortical responses to restraint than did their HS line counterparts. The LS quail also struggled much sooner and more often during the 5 min restraint period than did the HS ones. Collectively, these and previously reported line differences in behavioural, catecholamine and adrenocortical responsiveness are consistent with an interpretation based on the adoption of active and passive coping strategies respectively by LS and HS quail upon their exposure to alarming stimuli.

Adrenal Cortex↗
PubMed1996

Air quality in an animal facility: particulates, ammonia, and volatile organic compounds.

Concentrations of ammonia, volatile organic compounds, particles, and mouse allergen were measured in an animal facility. Ammonia concentrations averaged less than 1 ppm, below any health-based standards. The concentrations of volatile organic compounds were in the 5-15 micrograms/m3 range. Among the volatile organic compounds found, only the terpenes a-pinene and a-terpinol (which may be derived from the pine shavings used as bedding) were consistently present in concentrations greater than outdoor air. The primary air contaminant present at concentrations high enough to be of known physiological significance was the mouse allergen, Mus ml. To determine which activities in an animal room generated the highest concentrations of airborne Mus ml, a monitor that counted particles continuously was used. The particle counts were correlated with allergen levels in the worker's breathing zone (r50.83,p,0.05). Thus, a particle counter can be used effectively in an animal facility to identify specific activities that generate high levels of both particles and allergen. Such activities included changing mice from soiled to clean cages, cleaning floors, and changing foam inserts in pressurized individually ventilated cages. To reduce exposure to allergen during cage changing, which is the major activity for an animal caretaker, a capture-type ventilated changing table was designed and tested. Use of such a table reduced exposure to allergen in the worker's breathing zone from 4.961.1 to 2.160.3 ng Mus ml/m3, a level comparable to background levels.

Air Pollutants, Occupational↗