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Biomedical subjects

D Joseph

Publications and source records attributed to D Joseph.

At least 55 records · Page 3Linked to original sources
PubMed1999

Pre-operative chemoradiotherapy in locally advanced rectal cancer.

BACKGROUND: The aim of the present study was to investigate the effectiveness and toxicity of pre-operative chemoradiation in locally advanced rectal cancer (T3-T4). METHODS: Forty-seven patients were assessed (38 T3 and nine T4 tumours). Pre-operative pelvic radiotherapy was delivered in four fields, 45 Gy in 25 fractions over 5 weeks. Bolus 5-fluorouracil (5-FU) was delivered 500 mg/m2 on days 1, 2, 3 and days 22, 23, 24. Total mesorectal excision of the rectal tumour either by anterior or abdomino-perineal resection was planned at 4-6 weeks from completion of pre-operative treatment. Response to therapy was assessed by fresh macroscopic measurement of the surgical specimen. RESULTS: All patients undergoing chemoradiation completed therapy as planned, with no treatment-related interruptions. The regimen had a low acute toxicity profile with an estimated 50% or greater response in 38 out of 47 patients (four patients had complete responses). Forty-three (97%) of 44 patients who underwent surgery were operable. Patients who were operated on between 4 and 7 weeks had a statistically better response then those who were operated on after 7 weeks (P = 0.013; Fisher's exact test). Eight of 10 patients who were considered to be inoperable prior to the treatment underwent total mesorectal excision with negative radial margins. Anastomotic leakage occurred in four patients (9%); one required surgical intervention. Wound infection occurred in three patients (6%); one patient required re-exploration for haemorrhage. Delayed complications occurred in three patients (6%); one requiring surgery for a stomal stricture. After a median follow-up of 20 months, two patients (4%) had developed local recurrence. CONCLUSION: The pre-operative chemoradiation regimen employed had a low acute toxicity profile and all patients completed therapy. The majority of patients considered inoperable prior to receiving this treatment underwent successful excision. Appropriately fractionated pre-operative chemoradiotherapy is a reasonable option in this disease and deserves further evaluation.

Adenocarcinoma↗
PubMed1999

Simultaneous adjuvant radiotherapy and chemotherapy for stage I and II breast cancer.

The purpose of the present paper was to evaluate treatment outcome after conservative breast surgery or mastectomy followed by simultaneous adjuvant radiotherapy and cyclophosphamide, methotrexate and fluorouracil (CMF) therapy. Two hundred and sixty eight (268) patients were treated at two Australian and two New Zealand centres between 1981 and July 1995. One hundred and sixty-nine patients underwent conservation surgery and 99 had mastectomies. Median follow-up was 53 months. Conventionally fractionated radiation was delivered simultaneously during the first two cycles of CMF, avoiding radiation on the Fridays that the intravenous components of CMF were delivered. In conservatively treated patients, 5-year actuarial rates of any recurrence, distant recurrence and overall survival were 34.5 +/- 5.2%, 25.4 +/- 4.5% and 75.5 +/- 4.8%, respectively. Crude incidence of local relapse at 4 years was 6.3% and at regional/distant sites was 26.3%. Highest grades of granulocyte toxicity (< 0.5 x 10(9)/L), moist desquamation, radiation pneumonitis and persistent breast oedema were recorded in 10.7, 8.5, 8.9 and 17.2%, respectively. In patients treated by mastectomy, 5-year actuarial rates of any recurrence, distant recurrence and overall survival were 59.7 +/- 7.3%, 56.7 +/- 7.4% and 50.1 +/- 7%. The crude incidence of local relapse at 4 years was 5.6% and at regional/distant sites it was 45.7%. The issue of appropriate timing of adjuvant therapies has become particularly important with the increasing acknowledgement of the value of anthracycline-based regimens. For women in lower risk categories (e.g. 1-3 nodes positive or node negative), CMF may offer a potentially better therapy, particularly where breast-conserving surgical techniques have been used. In such cases CMF allows the simultaneous delivery of radiotherapy with the result of optimum local control, without compromise or regional or systemic relapse rates. Further randomized trials that directly address the optimal integration of the two modalities, such as the one carried out in Boston, are clearly necessary.

Adult↗
PubMed1999

Pre-operative chemo-radiotherapy in locally advanced rectal cancer: is this the way of future management?

The purpose of the present paper was to update a prospective analysis (H Elsaleh et al. unpubl. data, 1997) investigating the effectiveness and toxicity of pre-operative pelvic radiotherapy with modest dose 5-fluorouracil (5-FU) in locally advanced rectal cancer (T3-T4). A total of 31 patients were assessed (28 T3 and three T4 tumours). Pre-operative pelvic radiotherapy was delivered in four fields, 45 Gy to the International Commission on Radiation Units and Measurements (ICRU) point in 25 fractions over 5 weeks. A radiosensitizing dose of 5-FU was delivered at 500 mg/m2 on days 1, 2 and 3, and days 22, 23 and 24. Mesorectal excision of the rectal tumour either by anterior or abdomino-perineal resection was planned at 4-6 weeks from completion of pre-operative treatment. Response to therapy was assessed by fresh macroscopic measurement of the surgical specimen. Patients had a low toxicity profile; an estimated 50% or greater response was seen in 24 out of 31 (two complete responses). There were no surgical difficulties achieving resection. No late complications were documented, although follow-up was short. In locally advanced rectal cancer, pre-operative chemo-radiotherapy had a low toxicity profile. Appropriately fractionated pre-operative chemo-radiotherapy is a reasonable option in this disease and should be further evaluated. The optimal method of delivery of the radiosensitizing agent (5-FU) is the subject of further investigation.

Adult↗
PubMed1999

Inhaled nitric oxide does not improve cardiac or pulmonary function in patients with an exacerbation of chronic obstructive pulmonary disease.

OBJECTIVE: To determine whether inhaled nitric oxide (NO) improves right ventricular function in mechanically ventilated patients with severe chronic obstructive pulmonary disease (COPD). DESIGN: Open, prospective, controlled trial. SETTING: General intensive care unit of a community hospital. PATIENTS: Twelve patients with acute respiratory failure caused by acute exacerbation of COPD requiring mechanical ventilation. INTERVENTIONS: Insertion of a pulmonary artery catheter modified with a rapid response thermistor and a radial arterial catheter. Nitric oxide was then administered to the patient via a T piece placed between the Y piece of the ventilator and the endotracheal tube. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and gasometric variables were recorded before NO inhalation, during administration of inhaled NO (20 ppm, 20 mins), and 20 mins after NO discontinuation. Inhaled NO reduced pulmonary artery pressure from 26 +/- 6 to 22 +/- 5 mm Hg (p = .0004), but arterial oxygenation, cardiac output, and right ventricular ejection fraction remained unmodified (41% +/- 9% vs. 41% +/- 8%; not significant). Calculated pulmonary vascular resistance decreased from 453 +/- 233 to 348 +/- 108 dyne x sec/cm5 x m2 (p = .02), and right ventricular volumes did not change. Subsequently, right ventricular end-systolic pressure/volume ratio decreased from 0.52 +/- 0.22 to 0.44 +/- 0.19 mm Hg/mL/m2 (p = .01). No significant correlation was observed between the changes of pulmonary artery pressure (or pulmonary vascular resistance) and changes of right ventricular ejection fraction. CONCLUSION: Inhalation of NO does not seem to improve either right ventricular function or arterial oxygenation in patients with acute respiratory failure caused by acute exacerbation of COPD.

Administration, Inhalation↗
PubMed1999

Mucous-cell metaplasia and inflammatory-cell recruitment are dissociated in allergic mice after antibody- and drug-dependent cell depletion in a murine model of asthma.

Inflammatory-cell infiltration and epithelial modifications are prominent lesions of the bronchial mucosa in asthma and in experimental allergic bronchopulmonary inflammation. However, the recruitment of inflammatory cells and their relationship to the epithelial modifications and to functional alterations such as bronchopulmonary hyperreactivity (BHR) are less known. We studied the mechanisms of antigen-dependent inflammatory-cell recruitment to the lungs and the associated lesions and their relationship using drug- and antibody-dependent cell-depletion procedures. A single intranasal ovalbumin challenge in BP2 mice was found to induce hyperreactivity within 1 h after challenge, followed by the massive infiltration of immunoglobulin (Ig)E-bearing polymorphonuclear leukocytes (PMN), and eosinophils, and by a mucous-cell metaplasia of the bronchiolar epithelium. Similarly challenged BALB/c mice did not exhibit BHR, despite a moderate recruitment of inflammatory cells and mucous-cell metaplasia. Inflammatory-cell recruitment, mucous-cell metaplasia, and BHR were prevented by prior antibody-dependent depletion of CD3(+) lymphocytes and partially inhibited by the depletion of CD4(+) lymphocytes. Treatment with the granulocytopenic drug vinblastine before challenge completely abolished the recruitment of granulocytes without affecting the antigen-induced mucous-cell metaplasia. In this study two new key elements of the murine model of allergic pulmonary inflammation are described: the recruitment of IgE-bearing PMN between 3 and 72 h after challenge, and the dissociation between granulocytes and mucous-cell metaplasia.

Animals↗
PubMed1999

P53 alterations have no prognostic or predictive significance in Dukes' C rectal carcinomas.

We investigated the prognostic significance of p53 alterations in a consecutive series of 122 Dukes' C rectal carcinomas with a median patient follow-up period of 56 months. One third of patients were treated with post-operative adjuvant chemotherapy. Overexpression of p53 protein was observed in 42% (50/118) of cases using immunohistochemical analysis and mutation of the p53 gene in 38% (47/122) using single strand conformation polymorphism technique. Neither p53 overexpression nor mutation were associated with significantly worse patient survival in the overall group or in the subgroup of 35 patients who received standard post-operative chemotherapy with 5-fluorouracil and levamisole. Our results do not support the use of p53 alteration as a clinically useful prognostic marker for the overall survival of rectal cancer patients or for predicting their response to chemotherapy.

Adult↗
PubMed1998

Effect of ranitidine on gastric intramucosal pH in critically ill patients.

OBJECTIVE: To determine whether ranitidine a) increases the values of gastric intramucosal pH (pHi) in critically ill patients, as determined by tonometry; b) reduces the variability of these measurements. DESIGN: Prospective, double blind, randomized, placebo-controlled study. SETTING: General Intensive Care Unit of a teaching hospital. PATIENTS: Twenty-five critically ill, mechanically ventilated patients requiring arterial catheter and nasogastric tube. INTERVENTIONS: Tonometer placement; blind, random administration of intravenous ranitidine (50 mg) or placebo. MEASUREMENTS AND MAIN RESULTS: Tonometer saline PCO2 (PCO2i), arterial blood gases, gastric juice pH and pHi were determined immediately before, and 2, 4, 6 and 8 h after, ranitidine (12 patients) or placebo (13 patients). Ranitidine significantly increased gastric juice pH, but did not affect PCO2i or pHi; pHi was 7.34 +/- 0.14 before ranitidine, and 7.30 +/- 0.12, 7.31 +/- 0.11, 7.31 +/- 0.14 and 7.31 +/- 0.12-2, 4, 6 and 8 h, respectively, after ranitidine administration (p = 0.55). Ranitidine did not modify the coefficients of variation of PCO2i or pHi, either. No significant changes in gastric juice pH, PCO2i or pHi were observed in the placebo group. CONCLUSIONS: In critically ill patients, ranitidine has no effect on pHi values, and does not increase the reproducibility of pHi measurements.

APACHE↗
PubMed1998

Antihistaminic and antiallergic properties of dextro-mequitamium iodide in upper and lower guinea pig airways: comparison with azelastine.

1. The ability of dextro-mequitamium iodide (d-Meq) to antagonize bronchomotor and inflammatory effects mediated by histamine and antigen challenge in the upper or lower guinea pig airways or both and its potential activity against the recruitment and activation of eosinophils in the bronchial wall have been evaluated in comparison with azelastine. 2. In receptor-binding studies, d-Meq displayed a nanomolar affinity for H1 and muscarinic receptors, and it was endowed with potent bronchodilating properties in the nanomolar range toward tonic contractions induced by histamine and carbachol. 3. d-Meq (100-1,000 nmol/guinea pig) and azelastine (100-5,000 nmol/guinea pig) administered by aerosol significantly inhibited histamine- and antigen-induced increases in insufflation pressure in sensitized animals. 4. d-Meq (1,000-6,000 nmol/kg i.v.) dose dependently inhibited the histamine- or antigen-induced increase in vascular permeability in the upper airways. 5. d-Meq was more effective against histamine than antigen challenge, and its potency was similar or greater than that of azelastine. 6. Aerosolized d-Meq (1,000 nmol/animal) reduced antigen-induced eosinophil accumulation in the bronchoalveolar lavage (BAL) fluid from sensitized guinea pigs. 7. Eosinophils recovered from the BAL fluid of antigen-challenged animals showed an increased chemotaxis in response to LTB4 or platelet-activating factor. Both d-Meq and azelastine (300 nmol/animal) reduced this increase without affecting direct chemotaxis induced by leukotriene B4 (LTB4). 8. These findings provide evidence that local administration of d-Meq might be useful in the treatment of allergic disorders, such as rhinitis and asthma.

Animals↗
PubMed1998

Vomiting, retching, headache and restlessness after halothane-, isoflurane- and enflurane-based anaesthesia. An analysis of pooled data following ear, nose, throat and eye surgery.

BACKGROUND: Isoflurane has exceeded halothane and enflurane in usage. A literature search, however, revealed no data comparing the effects on emesis, headache and restlessness of these three agents. METHODS: With hospital ethics committee approval and patient consent, a prospective, randomised, double-blind study of 556 patients undergoing ENT and eye surgery was undertaken to evaluate the effects of halothane, isoflurane and enflurane on vomiting, retching, headache and restlessness until 24 h after anaesthesia. Balanced general anaesthesia was administered comprising benzodiazepine premedication, induction with thiopentone-atracurium-morphine (ENT patients) or fentanyl (eye patients), controlled ventilation and maintenance with either halothane 0.4-0.6 vol% (n = 186), isoflurane 0.6-0.8 vol% (n = 184) or enflurane 0.8-1 vol% (n = 186) in nitrous oxide 67% and oxygen. RESULTS: The three study groups were comparable, and comprised comparable subgroups having ear, nose, throat, intraocular and non-intraocular surgery. During early recovery from anaesthesia, the respective requirements for halothane, isoflurane and enflurane for analgesia (7%, 9% and 10%), frequency of emesis (6%, 8% and 8%), antiemetic requirements (1%, 1% and 2%), restlessness-pain scores and time spent in the recovery ward (27 SD 10, 31 SD 12 and 26 SD 9 min) were similar. During the ensuing 24-h postoperative period, patients who had isoflurane experienced emesis less often than those who had halothane (36% vs 46%, P < 0.025) but did so with similar frequency to those who had enflurane (46% vs 41%). Antiemetic requirements were least in those given isoflurane (isoflurane 12%, halothane and enflurane 23% each, P < 0.005), but headache and analgesic requirements were similar. CONCLUSION: Isoflurane induces less postoperative emesis than halothane, but headache is similarly frequent after anaesthesia with any of these agents.

Adult↗
PubMed1998

Postoperative adjuvant radiotherapy and 5-fluorouracil chemotherapy for rectal carcinoma.

Postoperative combined modality therapy with radiotherapy and 5-fluorouracil (5FU) chemotherapy is an effective adjuvant approach that reduces locoregional and distant metastatic disease in patients with high-risk rectal carcinoma. However, this approach results in a treatment regimen of at least 6 months' duration. The present prospective study investigates the integration of radiotherapy and 5FU chemotherapy in a protocol designed to minimize toxicity and reduce the overall treatment time. A total of 40 patients with TNM stage II or III disease received postoperative radiotherapy at four fractions per week with weekly 5FU bolus injections delivered on the fifth non-radiotherapy day. Patients also received systemic chemotherapy with leucovorin both before and after pelvic irradiation, with the total treatment duration extending for only 18 weeks. Patients were able to complete radiotherapy in 90% of cases, while the delivery of full-dose chemotherapy was achievable in the vast majority. The incidence of haematologic and gastrointestinal toxicities requiring the cessation of treatment was acceptable. With a median follow-up of 20.9 months among surviving patients, the estimated progression-free and overall survival at 2 years were 71% and 79%, respectively.

Adenocarcinoma↗
PubMed1997

Hyperbaric oxygen treatment for radiation proctitis.

PURPOSE: Our objective was to assess, retrospectively, the efficacy of hyperbaric oxygen treatment in radiation proctitis in all patients who have completed treatment for this disease at the Fremantle Hyperbaric Oxygen Unit. This unit is the only one of its kind in Western Australia. METHODS AND MATERIALS: Patients were assessed by a review of hospital records, blood bank records, and clinic review (if this was convenient), and all patients responded to a telephone survey. Patients were questioned regarding radiation proctitis symptoms and the degree to which each had improved. RESULTS: Most patients had previously been treated with radiotherapy for prostate carcinoma. Patients with proctitis mainly suffered from bleeding, diarrhoea, incontinence, and pain. In more than half of these patients, symptoms partially or completely resolved after hyperbaric oxygen treatment. CONCLUSION: Radiation-induced proctitis is a difficult clinical problem to treat and will probably become more significant with the rising incidence of diagnosis of prostate cancer. Hyperbaric Oxygen should be considered in the treatment of radiation-induced proctitis. Further prospective trials with strict protocol guidelines are warranted.

Female↗
PubMed1997

Saphenous vein covered stenting for right coronary artery lesion containing thrombus.

Vein covered stenting to close coronary pseudoaneurysm and perforation and in the setting of acute myocardial infarction have been described. This case report describes saphenous vein covered stenting to exclude a large thrombus in a right coronary artery lesion. Vein covered stenting may be considered as an option when dealing with a thrombus containing lesion.

Aneurysm, False↗
PubMed1997

Hemodynamic and gas exchange responses to inhalation of nitric oxide in patients with the acute respiratory distress syndrome and in hypoxemic patients with chronic obstructive pulmonary disease.

OBJECTIVE: Inhalation of nitric oxide (NO) can improve oxygenation and decrease mean pulmonary artery pressure (MPAP) in patients with the acute respiratory distress syndrome (ARDS). It is not known whether inhaled NO exerts a similar effect in hypoxemic patients with chronic obstructive pulmonary disease (COPD). DESIGN: Prospective clinical study. SETTING: General intensive care unit in Sabadell, Spain. PATIENTS: Nine mechanically ventilated COPD patients (mean age 72 +/- 2 years; forced expiratory volume in 1 s 0.91 +/- 0.11 l) and nine ARDS patients (mean age 57 +/- 6 years; mean lung injury score 2.8 +/- 0.1). MEASUREMENTS AND RESULTS: We measured hemodynamic and gas exchange parameters before NO inhalation (basal 1), during inhalation of 10 ppm NO (NO-10), and 20 min after NO was discontinued (in basal 2) in the ARDS group. In the COPD group, these parameters were measured before NO inhalation (basal 1), during different doses of inhaled NO (10, 20, and 30 ppm), and 20 min after NO was discontinued (basal 2). A positive response to NO was defined as a 20% increment in basal arterial partial pressure of oxygen (PaO2). MPAP and pulmonary vascular resistance (PVR) decreased significantly, while other hemodynamic parameters remained unchanged after NO-10 in both groups. Basal oxygenation was higher in the COPD group (PaO2/FIO2 (fractional inspired oxygen) 190 +/- 18 mmHg) than in the ARDS group (PaO2/FIO2 98 +/- 12 mmHg), (p < 0.01). After NO-10, PaO2/FIO2 increased (to 141 +/- 17 mmHg, p < 0.01) and Qva/Qt decreased (39 +/- 3 to 34 +/- 3%, p < 0.01) in the ARDS group. There were no changes in PaO2/FIO2 and Qva/Qt when the NO concentration was increased to 30 ppm in the COPD group. In both groups, a correlation was found between basal MPAP and basal PVR, and between the NO-induced decrease in MPAP and in PVR. The NO-induced increase in PaO2/FIO2 was not correlated with basal PaO2/FIO2. In the ARDS group, six of the nine patients (66%) responded to NO and in the COPD group, two of nine (22%) (p = 0.05). CONCLUSIONS: NO inhalation had similar effects on hemodynamics but not on gas exchange in ARDS and COPD patients, and this response probably depends on the underlying disease.

Administration, Inhalation↗
PubMed1997

Effect of sucralfate on gastric intramucosal pH in critically ill patients.

OBJECTIVE: To determine whether sucralfate administration affects the tonometric measurement of gastric intramucosal pH (pHi). DESIGN: Non-randomized observational study. SETTING: General intensive care unit of a teaching hospital. PATIENTS: Twenty critically ill, mechanically ventilated, consecutively admitted patients requiring an arterial catheter and nasogastric tube. INTERVENTIONS: Tonometer placement and sucralfate administration. MEASUREMENTS AND MAIN RESULTS: We simultaneously determined tonometer saline PCO2 (PCO2i), arterial blood gases, pH of gastric juice and pHi. These parameters were evaluated immediately before sucralfate administration, and 2 h and 4 h after. We did not detect any change in either PCO2i or pHi after sucralfate administration (PCO2i: basal 6.4 +/- 1.7, 2 h 6.3 +/- 1.7, 4 h 6.3 +/- 1.7; pHi: basal 7.35 +/- 0.13, 2 h 7.36 +/- 0.12, 4 h 7.36 +/- 0.12). CONCLUSIONS: Sucralfate does not affect the tonometric measurement of PCO2i and pHi.

Adult↗
PubMed1997

Short-term effects of prone position in critically ill patients with acute respiratory distress syndrome.

OBJECTIVE: Changing the position from supine to prone is an emerging strategy to improve gas exchange in patients with the acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate the acute effects on gas exchange, hemodynamics, and respiratory system mechanics of turning critically ill patients with ARDS from supine to prone. DESIGN: Open, prospective study. SETTING: General intensive care units. PATIENTS: 23 patients [mean age 56 +/- 17 (SD) years] who met ARDS criteria and had a Lung Injury Score > 2.5 (mean 3.25 +/- 0.3). INTERVENTIONS: The decision to turn a patient was made using a protocol based on impaired oxygenation despite the use of positive end-expiratory pressure and a fractional inspired oxygen (FIO2) of 1. MEASUREMENTS AND RESULTS: We measured gas exchange and hemodynamic variables in all patients and in 16 patients calculated respiratory system compliance when they were supine and 60 to 90 min after turning them to a prone position. This latter position was remarkably well tolerated and no clinically relevant complications or events were detected either during turning or while prone. The partial pressure of oxygen in arterial blood (PaO2)/FIO2 ratio improved from 78 +/- 37 mm Hg supine to 115 +/- 31 mm Hg prone (p < 0.001), and intrapulmonary shunt decreased from 43 +/- 11 to 34 +/- 8% (p < 0.001). Cardiac output and other hemodynamic parameters were not affected. Respiratory system compliance slightly improved from 24.7 +/- 10.2 ml/cmH20 supine to 27.8 +/- 13.2 ml/cmH20 prone (p < 0.05). An improvement in PaO2/FIO2 of more than 15% from changing from supine to prone was found in 16 patients (responders). Responders had more hypoxemia (PaO2/FIO2 70 +/- 23 vs 99 +/- 53 mm Hg in non-responders, p < 0.01), more hypercapnia (partial pressure of carbon dioxide in arterial blood (70 +/- 27 vs 64 +/- 9 mm Hg, p < 0.01) and a shorter elapsed time to the onset of ARDS and turning to the prone position (11.8 +/- 16 vs 32.8 +/- 42 days, p < 0.01). CONCLUSIONS: Turning critically ill, severely hypoxemic patients from the supine to the prone position is a safe and useful therapeutic intervention. Our data suggest that prone positioning should be carried out early in the course of ARDS.

Adult↗
PubMed1997

Scintigraphic evaluation of obstructing primary megaureter with Tc-99m MAG3.

Two children with the antenatal diagnosis of hydronephrosis secondary to a primary obstructed megaureter are presented. Both children were treated nonoperatively. They were observed with serial diuretic scintigrams using Tc-99m MAG3 and renal sonography. Throughout, the children have been asymptomatic. During a 3-year follow-up period, the diuretic renogram documented resolution of obstruction in one child and stable renal function with improved drainage in the other.

Child, Preschool↗