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D Joseph

Publications and source records attributed to D Joseph.

At least 73 records · Page 4Linked to original sources
PubMed1997

Rapid increase in bone-marrow eosinophil production and responses to eosinopoietic interleukins triggered by intranasal allergen challenge.

To define the effects of immunization and exposure to allergen on the eosinophil lineage, we studied blood and bone-marrow eosinophil numbers, serum interleukin (IL)-5 levels, and eosinophil progenitor and precursor responses to IL-3 and IL-5 in ovalbumin-immunized BALB/c mice after intranasal challenge. Increased blood eosinophilia was found in immune relative to nonimmune mice, but the differences between challenged and unchallenged immune animals were not significant. In contrast, significantly increased circulating levels of IL-5 and numbers of bone-marrow eosinophils were found in sensitized animals exposed to allergen, relative to unchallenged, sensitized controls. An allergen-induced increase in IL-3-sensitive progenitors yielding eosinophil-bearing colonies was also found at 2 h after challenge. Furthermore, an eosinophil differentiation assay showed a marked increase in the magnitude of the responses to IL-5 and IL-3 over a 7-day period in bone-marrow cells of sensitized animals, which was detectable at 24 h after allergen challenge, but not at 2 h and not in unchallenged controls. Modulation of the responses of bone-marrow cells to IL-5 is induced by a circulating factor present in challenged immune animals, as shown by in vivo plasma transfer, but is at best only partly blocked by in vivo treatment with the anti-IL-5 antibody TRFK-5. These data indicate that allergen challenge in the airways leads to rapid long-term modifications in bone-marrow eosinophil progenitors and precursors, and that increased responses to eosinopoietins in bone marrow depend on the release, between 2 h and 24 h after challenge, of a circulating factor distinct from IL-5.

Administration, Intranasal↗
PubMed1997

Stimulation of early eosinophil progenitors by a heat stable alveolar macrophage product from ovalbumin-sensitized and non-sensitized guinea pigs.

BACKGROUND: Alveolar macrophages (AM) may participate in brochopulmonary hyper-reactivity by secreting cytokines that recruit mature eosinophils, or induce eosinophil production from recruited circulating progenitors. OBJECTIVE: To define whether AM products can contribute to lung eosinophil production in immunized guinea pigs (GP), by analysing the effect of AM culture supernatants (AM-SN) on in vitro eosinophilopoiesis. METHODS: Liquid and semi-solid bone marrow (BM) cultures were seeded with SN from 95% pure AM exposed to LPS. RESULTS: AM-SN increased very significantly the long-term viability, cell proliferation and eosinophil production in liquid culture and supported formation of eosinophil-bearing mixed colonies, by acting on progenitors depleted of mature eosinophils. The effect on eosinophil production was not duplicated by natural or recombinant sources of GM-CSF (which nevertheless supported GM colony formation by GP BM), not by rhIL-8 (which was active on GP cells) and was not due to residual LPS. FPLC separation of active AM SN yielded a peak of apparent m.w. 43 kDa, active on both liquid and semi-solid cultures. The active moiety was heat- and trypsin-resistant. Neutralizing monoclonal antibodies to hGM-CSF, mGM-CSF, hIL-3 and mIL-3 failed to deplete the activity in AM-SN. Ovalbumin immunization induced its production by AM even without LPS challenge. CONCLUSIONS: The lack of T lymphocytes among factor-producing AM, the properties of the active material, the inability of GM-CSF to reproduce these effects, and the failure of MoAbs to GM-CSF and to IL-3 to neutralize the activity indicate it is not due to the major eosinopoietic factors GM-CSF, IL-3 or IL-5.

Animals↗
PubMed1997

Increased risk in esophageal obstruction with slow-release medications.

Although medication-induced (pill) esophagitis has been recognized for a long time, little data are available on the risk of recently introduced slow-release medications. These formulations may have an obstructive capability (undissolved medication blocking an obstructed lumen) or may cause tissue irritation (continuous leakage from a slowly disintegrating pill). We observed a patient with esophageal carcinoma who developed complete obstruction when three Procardia XL (nifedipine) extended-release tablets blocked the narrowed lumen. An intact Procardia XL tablet and a washed shell as a control were implanted subcutaneously in a rat. The intact pill produced a large inflammatory mass: in contrast, no inflammatory response was noted at the control site implanted with a washed shell. In vitro testing of seven different slow-release medications revealed a wide difference in their solubility at a neutral pH and in gastric juice of pH 1.8 (simulation of esophageal or gastric environment). Theolair-SR (anhydrous theophylline, sustained-release) tablets had the highest obstructive, but no irritating potential. Cardizem SR (diltiazem hydrochloride) sustained-release capsules dissolved promptly without obstructive potential. Adalat CC (nifedipine) extended-release tablets also dissolved early at both pH values. Cardizem CD (diltiazem hydrochloride) extended-release capsules and Calan SR (verapamil hydrochloride) sustained-release oral caplets disintegrated into granules that had a low obstructive potential, but their prolonged presence increased the risk of tissue irritation. Ecotrin (enteric-coated aspirin) tablets had a high obstructive and no irritating potential in the first 24 hours, after which they disintegrated and directly contacted the tissue. Procardia XL extended-release tablets had an insoluble shell that continued to leak a tissue-irritating content even after 48 hours, generating a prolonged obstructive and irritating condition. In conclusion, slow-release medications greatly increase the risk of esophageal injury. Their obstructive and tissue-irritating potentials differ widely. Slow-release formulations should be contraindicated in patients who have obstructive esophageal and gastric disorders.

Aged↗
PubMed1996

Timing of radiotherapy and chemotherapy following breast-conserving surgery for patients with node-positive breast cancer. International Breast Cancer Study Group.

PURPOSE: A controversy exists regarding whether it is safe to delay radiation therapy until the completion of chemotherapy following breast-conserving surgery for patients with node-positive breast cancer. Within the context of two concurrent randomized clinical trials we had the opportunity to evaluate outcomes for patients who received breast irradiation after completing different durations of chemotherapy. METHODS AND MATERIALS: From July 1986 to April 1993 the International Breast Cancer Study Group (IBCSG) Trial VI randomly assigned 1554 pre/perimenopausal node-positive breast cancer patients to receive cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) for either three consecutive courses on months 1-3, or six consecutive courses on months 1-6, both with or without reintroduction CMF. IBCSG Trial VII randomly assigned 1266 postmenopausal node-positive breast cancer patients to receive tamoxifen for 5 years, or tamoxifen for 5 years with three early cycles of CMF, both with or without three courses of delayed CMF. Both trials allowed a choice of mastectomy, or breast-conserving surgery plus radiation therapy, and both were stratified by type of surgery. Radiotherapy was delayed until the initial block of CMF was completed; 4 or 7 months after surgery for pre/perimenopausal patients, and 2 or 4 months after surgery for postmenopausal patients. Over both trials, 718 eligible patients elected to receive breast-conserving surgery plus radiation therapy: 433 on Trial VI, and 285 on Trial VII. Four-year actuarial total failure rates (failure at any site), risks of developing distant metastases (DM at any time during observation), and overall survival (OS) were estimated using the Kaplan-Meier method. To avoid potential bias due to competing causes of failure, only patients who could be followed for at least 4 years (enrolled prior to July 1, 1990) were used to evaluate the patterns of first relapse site. Crude percents of local failure with or without other sites (LF), distant metastases including regional nodal failure (DM/RNF), or other first events (second primaries/death without recurrence) were estimated for each treatment group. For this report, an intent to treat analysis was performed at a median follow-up of 48 months. RESULTS: No differences were found in the 4-year actuarial total failure rates, risk of developing distant metastases, and overall survival among the two radiotherapy groups of each study. The cumulative incidence of types of first failure and the 4-year crude rates showed no treatment differences in the patterns of site of first event. Estimates for the 4-year crude percent of local failures were 8 and 9% for pre/perimenopausal patients who had radiation therapy at 4 or 7 months after surgery, and 3 and 6% for postmenopausal patients who had radiation therapy at 2 months or 4 months after surgery. CONCLUSIONS: For node positive patients receiving breast-conserving surgery followed by radiation therapy, the incidence of breast recurrence in the conserved ipsilateral breast within 4 years was between 8 and 9% for pre/perimenopausal patients and between 3 and 6% for postmenopausal patients. After 48 months of median follow-up, administering radiation therapy after three or six cycles of CMF for pre/perimenopausal women, or after no cycles or three cycles of CMF for postmenopausal women does not influence overall efficacy or local control in this series.

Adult↗
PubMed1996

Radiotherapy for early infradiaphragmatic Hodgkin's disease: the Australasian experience.

PURPOSE: To review the Australasian results of Stage I and IIA Infradiaphragmatic Hodgkin's Disease (IHD) treated solely by irradiation. METHODS AND MATERIALS: Eligible patients had IHD only and were treated by irradiation with curative intent over the period of 1969 to 1988. Ten radiation oncology centres from within Australia and New Zealand were surveyed for patient, tumour and treatment variables. Disease free rates, survival and complications were analysed. RESULTS: 106 patients with IHD were studied. The average potential follow up was 9.4 years. The male to female ratio was 3.3:1. The median age was 37.5 years. Histological subgroups were as follows; lymphocyte predominant 43%, mixed cellularity 21%, lymphocyte depleted 5%, nodular sclerosing 27% and unclassifiable 4%. Fifty nine patients had laparotomy of which 22 (37%) were positive for tumour. Nine laparotomies were performed for diagnosis and the remainder for staging. One patient was up-staged by laparotomy and three were down-staged. Sixty-eight patients presented with inguinal disease alone, five with abdominal disease alone, 19 with two sites of involvement and 12 with inguinal, pelvic and abdominal disease. In two patients the site was unknown. There was no correlation between site of involvement, age, sex or histological subtype. Forty seven cases were clinically staged (CS) as follows: CS IA-23, CS IIA-24. The other 59 were pathologically staged (PS) as follows: PS IA-37, PS IB-1, PS IIA-21. Treatment consisted of involved field alone (16), inverted Y (68), inverted Y and spleen (13), para-aortic irradiation only (3), or total nodal irradiation (6). Mean dose was 37 Gy. There were 30 recurrences to give an acturial 10-year disease-free rate of 70%. In multivariate analysis lower number of tumour sites, lymphocyte predominant histology and higher dose were all significantly correlated with higher disease free rates. Eight patients died of Hodgkin's disease and 19 of other causes. The 10-year overall survival rate was 71%. Older age and higher number of disease sites were significantly correlated with shorter survival. Fourteen of 30 relapses may have been avoidable by the use of total nodal irradiation. In particular ten of 21 patients with abdominal disease relapsed in nodal sites which would have been covered by total nodal irradiation. CONCLUSIONS: The rate of control in IHD could perhaps be improved by avoiding involved field irradiation or by aggressive therapy with total nodal irradiation or combined modality chemo-irradiation in Stage II disease. Staging laparotomy does not appear to be indicated.

Abdominal Neoplasms↗
PubMed1996

The development of a provincial radiation oncology service: the first year report and its implications for future developments.

This study compares the actual first year's workload of a new radiation oncology department with that predicted, and assesses the impact of the differences, and their implications for future similar developments. The treatment records and diaries for the Geelong Hospital Radiation Oncology Department were reviewed after the first 12 months of operation (opened in June 1992). Statistics relating to the number of patients seen, number treated, diagnosis, etc., were evaluated and compared to the original estimates based upon population statistics and likely referral rates. Nine hundred and seven new patients were seen in this period, and from them 718 courses of treatment were initiated. One hundred and eighty-nine cases (20% of referrals) were seen but not treated. A further 102 treatment courses (14% of total) were initiated upon patients who had previously been irradiated. Forty-six per cent of patients were managed by 10 fractions or fewer, and a further 23% by 25 or more fractions. Eighty per cent of patients were managed by one or two fields. Electrons were used in only 14% of cases. Further calculations suggested a further possible 441 cases of referral could be expected, based upon current population statistics. Referral rates for radiation oncology are highly dependent on a number of factors. As a result, estimates of referrals and hence the size of a department required for a given population vary widely. Our data support these concepts, and the concept that referral is also strongly dependent upon the distance patients need to travel. In considering the development of units outside of major cities it is suggested that referrals are likely to be on the high side of estimates and a minimum two-machine unit is essential to cover the given workload.

Female↗
PubMed1996

Rat histidine decarboxylase promoter is regulated by gastrin through a protein kinase C pathway.

The enzyme L-histidine decarboxylase (HDC; EC 4.1.1.22), which converts L-histidine to histamine, plays a key role in the regulation of acid secretion. In the rat and human stomach, the peptide hormone gastrin appears to be one of the main regulators of HDC expression. In rats, marked elevation of gastric HDC mRNA abundance was observed within 12 h after induction of hypergastrinemia by a single injection of the proton-pump blocker omeprazole. In situ hybridization revealed that HDC expression occurred in the basal third of gastric glands where enterochromaffin-like cells are localized. To study the regulation of HDC gene transcription, 1,291 nucleotides of the 5'-flanking region of the rat HDC gene and the noncoding portion of exon 1 were cloned and sequenced. Gastrin and cholecystokinin (CCK) octapeptide equipotently stimulated the transcriptional activity of the rat HDC promoter three- to fourfold, and deletion analysis revealed the presence of a gastrin response element within 201 nucleotides upstream of the translational start site. Time-course studies revealed maximal activation of the HDC promoter after 12-36 h. Direct stimulation of protein kinase C (PKC) with the phorbol ester phorbol 12-myristate 13-acetate (PMA) substantially elevated rat HDC promoter activity, whereas induction of Ca2+ -dependent signaling pathways with thapsigargin was without effect. Downregulation or blockade of PKC abolished the effects of gastrin and PMA on the HDC promoter. These data indicate that stimulation of the CCK-B/gastrin receptor activates the rat HDC promoter in a time- and dose-dependent fashion and that this effect is primarily mediated via a PKC-dependent signaling pathway. Use of HDC as a model gene will allow further investigation of the intracellular pathways that are involved in gastrin-dependent gene regulation.

Animals↗
PubMed1996

A questionnaire study of 138 patients with restless legs syndrome: the 'Night-Walkers' survey.

After verifying the diagnosis of restless legs syndrome (RLS) in 105 patients who are part of a nationwide support group, we undertook a telephone survey of their symptomatology. We then compared the answers with those of 33 of our own RLS patients who had undergone a neurologic examination and had a periodic limb movement in sleep (PLMS) index of > 5 (number per hours of sleep). Although RLS has generally been considered to be a condition of middle to older age, the results for the support group, and for our patients, are similar in that more than a third of the patients in each group experienced their first symptoms before the age of 10. Initial lack of diagnosis or misdiagnosis by a physician were common and the symptoms were commonly thought to be psychogenic whatever the age of onset. In some cases, young age-onset RLS was severe from the start. For younger age-onset patients whose symptoms were severe enough to seek immediate medical attention, confounding or misdiagnosis included "growing pains" and attention deficit hyperactivity disorder. However, medical attention was generally not sought until the fourth decade. Most respondents stated that this was because their symptoms were mild at onset and then progressed. In the older age-onset patients, misdiagnoses also included skin irritation, arthritis, and malingering. A total remission of symptoms of a month or more was present in at least 15% of the individuals in all groups surveyed. More than 50% of the respondents know of one or more first-degree relatives affected by RLS. Five of our 33 patients had RLS initially triggered either by diabetic peripheral neuropathy or lumbosacral radiculopathy.

Adult↗
PubMed1995

Immediate and reversible platelet inhibition after intravenous administration of a peptide glycoprotein IIb/IIIa inhibitor during percutaneous coronary intervention.

We studied the pharmacokinetic and pharmacodynamic properties of integrelin, a novel platelet glycoprotein IIb/IIIa receptor inhibitor, in patients undergoing elective percutaneous coronary intervention. Patients were randomized to placebo (n = 19) or to 1 of 4 integrelin dosing regimens (total n = 54) that were studied sequentially. All patients received aspirin and heparin. Patients were followed until discharge for the occurrence of adverse clinical events: death, myocardial infarction, coronary artery bypass surgery, repeat intervention, or recurrent ischemia. Bleeding was the primary safety end point. Frequent blood sampling was performed for adenosine diphosphate-induced platelet aggregations. Simplate bleeding times were performed. Adverse clinical events occurred less often in the integrelin-treated patients, although the overall numbers were too small to make a definitive statement as to clinical efficacy. There was no significant increase in serious bleeding among integrelin-treated patients. The 2 highest integrelin boluses (180 and 135 micrograms/kg) immediately (15 minutes after the bolus) provided > 80% inhibition of adenosine diphosphate-induced platelet aggregation in > 75% of treated patients. A constant integrelin infusion of 0.75 micrograms/kg/min maintained this marked antiplatelet effect, whereas an infusion of 0.50 micrograms/kg/min allowed gradual recovery of platelet function. Elective coronary intervention was performed safely and with no significant increase in serious bleeding events using integrelin with aspirin and heparin as an antithrombotic regimen. Integrelin provided rapid, intense, and persistent ex vivo platelet inhibition during coronary intervention. This new antiplatelet agent may be beneficial in reducing platelet-mediated ischemic complications of percutaneous coronary intervention.

Aged↗
PubMed1995

[Selective pulmonary vasodilator effect of inhaled nitric oxide in a patient with pulmonary thromboembolism].

The increase in pulmonary vascular resistences in acute pulmonary thromboembolism (APT) is the consequence of anatomical obstruction and pulmonary artery constriction. The administration of inhaled nitric oxide (NO) may be therapeutically useful in acute pulmonary hypertension by APT given its limited vasodilator effect on pulmonary circulation. A patient with APT in whom this selective vasodilator effect was observed is presented. The authors suggest that the administration of inhaled NO may be a potentially beneficial coadjuvant therapy in acute pulmonary hypertension induced by APT.

Administration, Inhalation↗
PubMed1995

A phase III study of accelerated radiotherapy with and without carboplatin in nonsmall cell lung cancer: an interim toxicity analysis of the first 100 patients.

PURPOSE: In 1989 we initiated a multicenter randomized trial to determine if accelerated radiotherapy with or without concurrent carboplatin improves local control and survival in patients with limited nonsmall cell lung cancer. This interim analysis was performed on the first 100 patients to determine whether the toxicity of the four treatment arms is acceptable. METHODS AND MATERIALS: One hundred patients with limited nonsmall cell lung cancer have been randomized to receive one of four treatments: arm I, radiotherapy 60 Gray (Gy) in 30 fractions in 6 weeks; arm II, accelerated radiotherapy 60 Gy in 30 fractions in 3 weeks; arm III, radiotherapy as in arm I plus carboplatin 350 mg/m2 during weeks 1 and 5 of radiotherapy; arm IV, radiotherapy as in arm II plus carboplatin 350 mg/m2 during week 1. Survival was measured for the group as a whole and treatment-related toxicities in the four arms were compared. RESULTS: The estimated median survival for all 100 patients was 17.1 months with 33% estimated survival at 2 years. The major toxicities were hematologic and esophageal. Patients receiving carboplatin had more neutropenia (p < 0.0001) and thrombocytopenia (p = 0.002) than patients receiving radiotherapy alone, and this was most marked in patients on arm III. Both carboplatin and accelerated radiotherapy separately caused more severe esophagitis when compared to conventional radiotherapy alone (p = 0.011 and p = 0.0017, respectively). Esophagitis was more prolonged in patients having accelerated radiotherapy (p < 0.0001, median duration 3.2 months compared with 1.4 months for patients receiving conventional fractionation). Six patients (23%) treated on arm II have required dilatation of esophageal stricture, one dying with a laryngo-esophageal fistula. CONCLUSION: In patients receiving radiotherapy for unresectable lung cancer, overall treatment time can be halved and carboplatin administered concurrently with increased but acceptable esophageal and hematologic toxicity.

Adult↗
PubMed1995

Radiation therapy for early stage Hodgkin's disease: Australasian patterns of care. Australasian Radiation Oncology Lymphoma Group.

PURPOSE: Analysis of treatment outcome for Stage I-IIA supradiaphragmatic Hodgkin's disease treated solely by irradiation in Australia and New Zealand. METHODS AND MATERIALS: Patients with supradiaphragmatic Hodgkin's disease only who were treated by irradiation alone with curative intent between 1969 to 1988 were retrospectively reviewed. Ten radiation oncology departments in Australia and New Zealand contributed patient data to the study. Patient, tumor, and treatment variables were recorded. Disease-free interval, survival, and complications were analyzed. RESULTS: Eight hundred and twenty patients were reviewed. The median age was 29 years. There were 437 men and 383 women. The distribution of 310 clinically staged patients was 170 stage IA, 5 IB, and 135 IIA. Five hundred and ten patients received laparotomies, and pathologic staging was as follows: IA 214, IB 13, IIA 283. The 10-year actuarial disease-free rate was 69% and overall survival rate was 79%. Increasing age, male sex, higher number of involved sites, the use of involved field irradiation, no staging laparotomy, and earlier year of treatment were significantly associated with an increased risk of relapse and lower survival. Actuarial 10-year survival following recurrence was 48%. Acute complications requiring interruption to treatment occurred in 46 patients (6%), but < 1% had their treatment permanently suspended. Actuarial complication rates at 10 years were: cardiac 2%, pulmonary 3% and thyroid 5%. There were 44 second malignancies including 10 non-Hodgkin's lymphomas, 3 leukemias, 7 lung, and 6 breast cancers. Mean delay to the development of a second cancer was 6 years. The 10-year actuarial rate of second malignancy was 5%. CONCLUSIONS: The Australasian experience of early stage Hodgkin's disease is consistent with the results in the published literature and confirms that irradiation produces a high cure rate with minimal toxicity.

Adult↗
PubMed1995

Catheter-induced "accordion effect" in tortuous right external iliac artery during peripheral angiography.

Mechanical distortion of tortuous coronary arteries mimicking spasm or dissection during percutaneous transluminal coronary angioplasty due to balloon guidewire systems has previously been reported. This case reports a similar phenomenon in the peripheral vascular system induced by a diagnostic catheter. Recognition of this pseudo lesion may help to avoid complications and unnecessary intervention.

Angiography↗
PubMed1995

Control of sexually transmitted diseases in Haiti: results and implications of a baseline study among pregnant women living in Cité Soleil Shantytowns.

Women attending Haitian slum-based antenatal clinics were evaluated for sexually transmitted diseases (STDs): 110 (11%) of 996 were syphilis seroreactive, 313 (35%) of 903 had trichomoniasis, 110 (12%) of 897 had gonococcal or chlamydial cervical infection (or both), and 418 (47%) of 891 had at least one STD. Syphilis seroreactivity was associated with illiteracy (P = .007), lower socioeconomic status (P < .001), and a history of spontaneous abortion (P = .02). Of 663 evaluated sera, 56 (8%) had human immunodeficiency virus (HIV) antibodies. In multivariate analysis, positive HIV serostatus was associated with syphilis seroreactivity (P = .006), partner's unemployment (P = .002), and history of a previous sex partner (P = .04). Risk factors for gonococcal or chlamydial cervical infection were evaluated. Clinical assessment of cervical discharge, a World Health Organization algorithm, and a decision model based on local risk factors were 64%, 77%, and 89% sensitive, respectively, and 44%, 38%, and 43% specific, respectively, for predicting cervical infection. Alternative treatment approaches should be validated while waiting for affordable, simple, rapid, and accurate laboratory diagnostic tests for gonococcal and chlamydial cervical infections.

Abortion, Spontaneous↗
PubMed1995

Calibration of entrance dose measurement for an in vivo dosimetry programme.

An increasing number of cancer treatment centres are using in vivo dosimetry as a quality assurance tool for verifying dosimetry as either the entrance or exit surface of the patient undergoing external beam radiotherapy. Equipment is usually limited to either thermoluminescent dosimeters (TLD) or semiconductor detectors such as p-type diodes. The semiconductor detector is more popular than the TLD due to the major advantage of real time analysis of the actual dose delivered. If a discrepancy is observed between the calculated and the measured entrance dose, it is possible to eliminate several likely sources of errors by immediately verifying all treatment parameters. Five Scanditronix EDP-10 p-type diodes were investigated to determine their calibration and relevant correction factors for entrance dose measurements using a Victoreen White Water-RW3 tissue equivalent phantom and a 6 MV photon beam from a Varian Clinac 2100C linear accelerator. Correction factors were determined for individual diodes for the following parameters: source to surface distance (SSD), collimator size, wedge, plate (tray) and temperature. The directional dependence of diode response was also investigated. The SSD correction factor (CSSD) was found to increase by approximately 3% over the range of SSD from 80 to 130 cm. The correction factor for collimator size (Cfield) also varied by approximately 3% between 5 x 5 and 40 x 40 cm2. The wedge correction factor (Cwedge) and plate correction factor (Cplate) were found to be a function of collimator size. Over the range of measurement, these factors varied by a maximum of 1 and 1.5%, respectively. The Cplate variation between the solid and the drilled plates under the same irradiation conditions was a maximum of 2.4%. The diode sensitivity demonstrated an increase with temperature. A maximum of 2.5% variation for the directional dependence of diode response was observed for angle of +/- 60 degrees. In conclusion, in vivo dosimetry is an important and reliable method for checking the dose delivered to the patient. Preclinical calibration and determination of the relevant correction factors for each diode are essential in order to achieve a high accuracy of dose delivered to the patient.

Female↗
PubMed1994

Antibody to very late activation antigen 4 prevents antigen-induced bronchial hyperreactivity and cellular infiltration in the guinea pig airways.

This report examines the effect of an anti-VLA-4 monoclonal antibody (mAb) HP1/2 on antigen-induced bronchial hyperreactivity to methacholine, and on eosinophil and T lymphocyte infiltration in the airways of guinea pigs sensitized and challenged by aerosolized ovalbumin and used 24 h thereafter. The intravenous administration of 2.5 mg/kg of HP1/2, but not of its isotype-matched mAb 1E6, 1 h before and 4 h after antigen inhalation, markedly inhibited the increased bronchopulmonary responses to intravenous methacholine, as well as airway eosinophilia in bronchoalveolar lavage (BAL) fluid and in bronchial tissue. HP1/2 also suppressed the antigen-induced infiltration of the bronchial wall by CD4+ and CD8+ T lymphocytes, identified by immunohistochemical technique using specific mAbs that recognize antigenic epitopes of guinea pig T cells. Treatment with HP1/2 also resulted in a significant increase in the number of blood eosinophils, suggesting that inhibition by anti-VLA-4 mAb of eosinophil recruitment to the alveolar compartment may partially account for their accumulation in the circulation. These findings indicate that eosinophil and lymphocyte adhesion and subsequent infiltration into the guinea pig airways that follow antigen challenge are mediated by VLA-4. Furthermore, concomitant inhibition of antigen-induced bronchial hyperreactivity and of cellular infiltration by anti-VLA-4 mAb suggests a relationship between airway inflammation and modifications in the bronchopulmonary function.

Animals↗