Public Service Award: Joe Garagiola.
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Awards and Prizes↗
Biomedical subjects
R B Jones
Publications and source records attributed to R B Jones.
Do agoraphobics interpret the environment in large shops and supermarkets differently?
Agoraphobics typically have difficulties in visiting supermarkets. The brief report presents results of a survey investigating the properties of supermarkets which provoke or ease anxiety-related responses in shoppers (N = 500) and two further groups: agoraphobics (N = 40) and participants responding to a local press advert (N = 54). Results showed that layout features, stairways and diminished access were rated as more anxiety provoking in the agoraphobic-type groups compared to general shoppers. The safety-signal model of agoraphobic behaviour was supported although some evidence of dysfunction of spatial orientation was found.
Activities of Daily Living↗
Species-, serogroup-, and serovar-specific epitopes are juxtaposed in variable sequence region 4 of the major outer membrane proteins of some Chlamydia trachomatis serovars.
Synthetic peptides and murine monoclonal antibodies were used to map cross-reactive chlamydial epitopes. A species-specific epitope in the central region of variable sequence region 4 abuts the amino-terminal end of a B-serogroup-specific or F/G-serogroup-specific epitope, which in turn abuts known serovar-specific epitopes. The carboxyl-terminal portion of variable sequence region 4 (residues 297 to 314) comprises a region of end-to-end B-cell epitopes in some serovars of the B and F/G serogroups.
Amino Acid Sequence↗
Chlamydial cervicitis and urethritis: single dose treatment compared with doxycycline for seven days in community based practises.
STUDY GOAL: To compare the efficacy and safety of single 1 g oral azithromycin with doxycycline, 100 mg twice daily for seven days for treatment of uncomplicated urogenital chlamydial infection. STUDY DESIGN: Randomised, unblinded, comparative trial, involving 597 patients demonstrating clinical evidence of genital chlamydia and a positive non-culture assay for Chlamydia trachomatis. RESULTS: Among the azithromycin- and doxycycline-treated patients 61% and 60%, respectively, were asymptomatic within one week after the first dose. At two weeks, these figures increased to 86% and 83%, respectively. Bacteriological eradication, based on a negative assay, occurred in 338 (97%) of 347 azithromycin-treated patients and 161 (99%) of 163 doxycycline-treated patients. CONCLUSION: Treatment of uncomplicated chlamydial cervicitis and urethritis with single 1 g oral azithromycin is equivalent to standard therapy with doxycycline. Drug-related adverse events were approximately twice as common as previously reported for both drugs.
Adolescent↗
High-dose paclitaxel, cyclophosphamide, and cisplatin with autologous hematopoietic progenitor-cell support: a phase I trial.
PURPOSE: To determine the maximal-tolerated dose (MTD) of paclitaxel in combination with high-dose cyclophosphamide (CPA) and cisplatin (cDDP) followed by autologous hematopoietic progenitor-cell support (AHPCS). PATIENTS AND METHODS: Forty-nine patients with poor-prognosis breast cancer, non-Hodgkin's lymphoma (NHL), or ovarian cancer were treated with escalating doses of paclitaxel infused over 24 hours, followed by CPA (5,625 mg/m2 intravenously over 1 hour in three divided doses) and cDDP (165 mg/m2 intravenously as a continuous infusion over 72 hours) and AHPCS. Pharmacokinetic measurements for each drug were performed. RESULTS: Dose-limiting toxicities were encountered in two patients at 825 mg/m2 of paclitaxel; one patient died of multiorgan failure that involved the lung, CNS, and kidneys, and the other developed grade 3 respiratory, CNS, and renal toxicity, which resolved. The MTD of this combination was determined to be paclitaxel 775 mg/m2, CPA 5,625 mg/m2, and cDDP 165 mg/m2 followed by AHPCS. Sensory polyneuropathy and mucositis were prominent toxicities, but both were reversible and tolerable. The pharmacokinetics of paclitaxel correlated significantly with the severity of mucositis (P < .001) and peripheral neuropathy (P < .00004). Eighteen of 33 patients (54%) with measurable, heavily pretreated metastatic breast cancer achieved a partial response (PR). Responses were also observed in patients with NHL (four of five patients) and ovarian cancer (two of two). CONCLUSION: It is possible to escalate the dose of paclitaxel to 775 mg/m2 in combination with 5,625 mg/m2 of CPA, 165 mg/m2 of cDDP, and AHPCS. An encouraging response rate in poor-prognosis patients with breast cancer, NHL, and ovarian cancer warrants further study.
Adult↗
High-dose chemotherapy with autologous hematopoietic progenitor cell support for metastatic and high-risk primary breast cancer.
High-dose chemotherapy (HDCT) is being evaluated in the treatment of metastatic and high-risk primary breast cancer. The actuarial 2-year disease-free survival rate for patients with stage IV breast cancer is approximately 15% to 20%. A single metastatic site and achievement of a complete response to induction chemotherapy may be favorable prognostic indicators for disease-free survival after HDCT. Phase II studies in patients with primary breast cancer and > or = 10 and four to nine involved axillary nodes are encouraging. Prospective randomized trials are ongoing in these patient groups. Various strategies are being investigated to reduce the incidence of relapse after HDCT.
Actuarial Analysis↗
Use of amifostine in bone marrow purging.
One of the main obstacles for the use of high-dose chemotherapy with autologous hematopoietic progenitor cell support in the treatment of malignancies is the possibility of reinfusing clonogenic tumor cells with the hematopoietic graft. Purging of the graft with chemicals can reduce the number of tumor cells but can also damage the normal hematopoietic progenitors. Preclinical studies showed that the phosphorylated sulfhydryl compound amifostine (WR-2721) can protect normal hematopoietic progenitors from damage from alkylating agents. We conducted a randomized clinical trial in patients with breast cancer, non-Hodgkin's lymphoma, and Hodgkin's disease undergoing autologous bone marrow transplant. In this study, patients were randomized to have their bone marrow purged with 4-hydroperoxycyclophosphamide (4-HC) with (arm A) or without (arm B) amifostine. The percentage of colony-forming unit granulocyte-macrophages recovered after purging was higher in the amifostine arm, both in patients with breast cancer and in those with lymphoma, although this difference was not statistically significant. In addition, the time to engraftment was significantly shorter in the amifostine arm in both cohorts. We showed that pretreatment of bone marrow with amifostine prior to purging with 4-HC can protect normal hematopoietic progenitors from damage by 4-HC. This resulted in shorter engraftment rates and less need for supportive care.
Adult↗
Infusional therapy with alkylating agents.
In 1990, Donehower editorialized in the Journal of the National Cancer Institute, entitled "Evaluating Cancer Chemotherapy by Infusion" (92). In the same issue, Goldberg reported a phase III study comparing etoposide and cDDP administered by either bolus or infusion to patients with non-small cell lung cancer (93). There was no advantage to the infusional schedule; in fact, it produced greater myelotoxicity. In the editorial, Donehower commented that the daily etoposide dose was not substantially pharmacokinetically different from a daily bolus schedule (because of the drug's relatively long half-life), and the greater myelotoxicity of infusional cDDP might have been predicted by preclinical studies. He suggested that studies of cancer drugs given by infusion should only be undertaken in the context of strong accompanying pharmacologic and preclinical experimental rationale, and that phase III studies of this concept should only be undertaken after a strong justification is developed. The concept that infusions of AA are generally less toxic than bolus dosing formed much of the rationale for infusional AA administered with BMT. The detailed studies of Teicher (1) and Frei (89), cited above, provided strong preclinical data suggesting that improvement in the therapeutic index could be achieved for most AA when infusional schedules were used. Additionally, the high toxic risk accompanying high-dose combination AA therapy with hematopoietic cell support mandated detailed PK studies. Data produced by these efforts (5, 12) now add additional basis for systemic exploration of AA infusions. Armed with the basic data suggested by Donehower, a more scientifically based study of AA infusion can take place in the future. Compelling rationales now support such studies. The availability of means to avoid fatal hematologic toxicity for virtually all patients suggests that the next era of exploration of AA infusions will be fruitful, and accompanied by a deeper understanding of the relationship between visceral organ toxicities and PK/PD changes produced by AA administered over prolonged periods.
Antineoplastic Agents, Alkylating↗
High-dose chemotherapy with AHPCS for the treatment of breast cancer. The University of Colorado results.
In summary, the administration of effective high-dose chemotherapy regimens at a time of minimal tumor burden should eradicate disease in selected breast cancer patients who otherwise have little chance of prolonged disease-free survival following standard-dose treatments. The results are particularly promising for breast cancer patients with high-risk stage II/III, and NED or responsive stage IV disease. Many studies to confirm these hypotheses are in progress. New high-dose chemotherapy regimens, together with methods to reduce tumor contamination of the graft and new treatment modalities should improve the current results in patients with breast cancer.
Antineoplastic Combined Chemotherapy Protocols↗
Paclitaxel-containing high-dose chemotherapy: the University of Colorado experience.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of the most important antineo-plastic agents developed over the last 20 years. It has proven activity in breast cancer, ovarian cancer, and non-small cell lung cancer. In this study, the possibility of incorporating paclitaxel into a high-dose chemotherapy regimen targeting patients with breast cancer was evaluated. From a widely used regimen composed of cyclophosphamide, cisplatin, and carmustine, carmustine was deleted and paclitaxel added at the beginning of the regimen. The dose of paclitaxel was then escalated until life-threatening toxicities occurred. It was demonstrated that the dose of paclitaxel could be escalated to 775 mg/m2, combined with cyclophosphamide 5,625 mg/m2 and cisplatin 165 mg/m2, followed by autologous hematopoietic progenitor cell support. A phase II study testing this combination in patients with chemotherapy-responsive metastatic breast cancer has been initiated. A new phase I study to test the feasibility of adding carmustine to this paclitaxel-based regimen is currently under way. The status of this study is briefly summarized.
Adult↗
CT determination of tibial tubercle lateralization in patients presenting with anterior knee pain.
Anterior knee pain is commonly associated with patellofemoral malalignment. Both conventional radiographic measurements and CT measurements have been proposed to define and confirm the sometimes difficult clinical diagnosis of anterior knee pain secondary to patellofemoral malalignment. Using CT imaging with computerized technique to measure anatomic relationships, we evaluated patients (n = 50) with anterior knee pain for excessive lateralization of the tibial tubercle. The symptomatic knee of each patient was compared with their asymptomatic knee as well as with the knees of patients with other causes of anterior knee pain (n = 10) and with the knees of asymptomatic controls (n = 10). The symptomatic knee of patients with suspected patellofemoral malalignment demonstrated significantly greater lateralization of the tibial tubercle (12.2 +/- 0.5 mm) than did the asymptomatic knee (9.0 +/- 0.7 mm). The symptomatic knees of patients with patellofemoral malalignment also demonstrated significantly greater lateralization of the tibial tubercle than did the knees of patients with other causes of anterior knee pain (5.9 +/- 0.9 mm). When a control population was added to the analysis, the patients with symptomatic patellofemoral malalignment demonstrated significantly greater lateralization of the tibial tubercle than did the controls (6.4 +/- 0.4 mm). Using a critical value of 9 mm lateralization, the CT diagnosis of patellofemoral malalignment had a specificity of 95% and a sensitivity of 85%. We conclude that CT determination of tibial tubercle position assists the diagnosis of patellofemoral malalignment.
Female↗
Open-field and tonic immobility responses in domestic chicks of two genetic lines differing in their propensity to feather peck.
1. The open-field and tonic immobility reactions of female domestic chicks of 2 genetic lines which showed high (HP) or low (LP) levels of feather pecking were compared. 2. Chicks of the LP line showed less freezing, and vocalised and walked sooner and more in the open field than did their HP counterparts. 3. There were no differences between lines in the durations of their tonic immobility responses, at least in the present study. 4. The pattern of results may reflect line divergence in underlying social motivation rather than fearfulness.
Animals↗
The effect of relative humidity on mouse allergen levels in an environmentally controlled mouse room.
To determine the effect of humidity on the levels of the mouse allergen Mus m 1, an experimental animal room was constructed to control environmental variables. The sex, strain, age, and number of mice was constant in the room, so that the average daily production of Mus m 1 would not vary greatly. Six different levels of relative humidity from 15% to 65% were maintained for a minimum of a week each. Daily collections of airborne particulates were eluted from filters and Mus m 1 content measured by immunological assay. Increasing relative humidity caused a decrease in Mus m 1 levels from a high of 3 ng/m3 at 15% humidity to a low of 0.5 ng/m3 at 65% humidity. Thus, reduction of airborne allergen levels can be achieved by careful attention to humidity control, especially during the winter heating season when humidity levels may be low. This experimental room can be used to measure the effect of other variables such as ventilation rate, caging, bedding, and work practices on the levels of mouse allergen in an animal facility.
Allergens↗
Large volume ex vivo expansion of CD34-positive hematopoietic progenitor cells for transplantation.
A large volume culture system was developed for the ex vivo expansion of CD34 positive (+) hematopoietic progenitors, using cell donated by 15 patients receiving high-dose chemotherapy with autologous hematopoietic progenitor cell support (AHPCS). Substantial expansion of myeloid (181-fold) and megakaryocyte (41-fold) progenitors cells was demonstrated, using the conditions that we determined to be optimal: CD34+ progenitors cultured unperturbed for 7 (marrow) or 10 (blood) days in Teflon-coated bags with X-Vivo-10 medium containing 10% autologous plasma, 100 ng/ml, respectively, of recombinant stem cell factor (SCF), interleukin 3 (IL-3), interleukin 6 (IL-6), and granulocyte colony-stimulating factor (G-CSF). The studies demonstrated that (a) CD34 selection was necessary to obtain large, clinically relevant numbers of hematopoietic progenitors, (b) the addition of G-CSF to the baseline regimen of SCF/IL-3/IL-6 significantly enhanced the expansion of myeloid progenitors, (c) the addition of IL-1 to SCF/IL-3/IL-6 did not significantly enhance myeloid progenitor cell expansion, (d) CD34+ G-CSF-mobilized peripheral blood progenitor cells (PBPC) produced higher numbers of myeloid progenitors in culture than CD34+ marrow cells, and (e) long-term tissue culture (LTC) assays demonstrate the preservation of long-term initiating cells in ex vivo culture. The short-term and long-term reconstituting capability of CD34+ PBPC cultured in this system remains to be determined and will be evaluated in a clinical trial where they will be used as the sole source of AHPCS following high-dose therapy.
Antigens, CD34↗
Stem cell isolation.
High-dose chemotherapy with autologous hematopoietic progenitor cell support is increasingly used to treat a variety of malignant diseases. A drawback of this technique is the potential for infusing clonogenic tumor cells with the autograft, producing relapse of the disease in the patient. The use of positive selection techniques to isolate stem cells and thus reduce or eliminate tumor cell contamination has been extensively studied over the past few years. Preliminary clinical results have demonstrated that these procedures deplete 2 to 7 logs of tumor cells and do not impair engraftment. It is too early to assess the ultimate clinical benefit of this strategy. Additional applications of CD34-selection include ex vivo expansion of and gene transfer into hematopoietic progenitor cells and T-cell depletion of allogeneic grafts to reduce the incidence of graft-versus-host disease.
Antigens, CD34↗
Rapid antigen detection assay for identification of Chlamydia trachomatis infection.
A rapid antigen detection test was compared with direct fluorescent-antibody staining and with tissue culture isolation for the detection of Chlamydia trachomatis infections in 507 women. The sensitivities observed were 75, 76, and 84%, respectively, with specificities of > 99%.
Antigens, Bacterial↗
Respiratory failure in acute pancreatitis.
There are a number of important pulmonary complications of acute pancreatitis which make a significant contribution to the morbidity and mortality of the condition. The pathophysiology and management guidelines are given for each and approaches towards better treatment in the future are discussed.
Acute Disease↗
Use of smokeless tobacco in the World Series, 1986 through 1993.
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Baseball↗