PubMed Health⌕ Search

Biomedical subjects

I Crocker

Publications and source records attributed to I Crocker.

At least 19 recordsLinked to original sources
PubMed2006

Taurine transporter in fetal T lymphocytes and platelets: differential expression and functional activity.

Transplacental transfer of taurine, a beta-amino acid essential for fetal and neonatal development, constitutes the primary source of taurine for the fetus. Placental transport of taurine is compromised in pregnancies complicated by intrauterine growth restriction, resulting in a reduced concentration of taurine in cord plasma. This could impact on fetal cellular metabolism as taurine represents the most abundant intracellular amino acid in many fetal cell types. In the present study, we have used pure isolates of fetal platelets and T lymphocytes from cord blood of placentas, from normal, term pregnancies, as fetal cell types to examine the cellular uptake mechanisms for taurine by the system beta transporter and have compared gene and protein expression for the taurine transporter protein (TAUT) in these two cell types. System beta activity in fetal platelets was 15-fold higher compared with fetal T lymphocytes (P < 0.005), mirroring greater TAUT mRNA expression in platelets than T lymphocytes (P < 0.005). Cell-specific differences in TAUT protein moieties were detected with a doublet of 75 and 80 kDa in fetal platelets compared with 114 and 120 kDa in fetal T lymphocytes, with relatively higher expression in platelets. We conclude that greater system beta activity in fetal platelets compared with T lymphocytes is the result of relatively greater TAUT mRNA and protein expression. This study represents the first characterization of amino acid transporters in fetal T lymphocytes.

Blood Platelets↗
PubMed2002

Effect of pregnancy and obstructive jaundice on inflammatory diseases: the work of P S Hench revisited.

Hench considered that cortisone improved inflammatory joint symptoms during pregnancy and obstructive jaundice. However, the improved symptoms are probably due to changes in the proportions of fatty acids in plasma and inflammatory cell phospholipids. These changes decrease the superoxide anions and eicosanoids produced and also reduce tumour necrosis factor alpha production.

Adrenal Cortex Hormones↗
PubMed2001

Treatment of long, diffuse, in-stent restenotic lesions with beta radiation using strontium 90 and sequential positioning "pullback" technique: procedural details and clinical outcomes.

BACKGROUND: Long, diffuse, in-stent restenotic lesions have been problematic for many patients, necessitating the need for multiple repeat percutaneous coronary interventions (PCI). The need for repeat PCI has been significantly reduced in patients since the advent of vascular brachytherapy. In-stent restenosis resulting in long lesions (> 30 mm) presents even more of a challenge. The interventional injury length created during PCI is usually greater than 30 mm and the vascular brachytherapy systems available in most hospitals are 30 mm or 40 mm in length. The purpose of this paper is to define "pullback technique" and to report the Montreal Heart Institute (MHI) data to show that the pullback technique using the Novoste system seems to be a safe and effective method for using vascular brachytherapy to treat long, diffuse, in-stent restenotic lesions. METHODS: We reviewed the database of patients enrolled in the Compassionate Use Registry between August 1999 and July 2000. The data are reported on 23 consecutive patients treated with the pullback technique. RESULTS: The mean lesion length was 49.4 +/- 19.8 mm. Three patients (13%) underwent target vessel revascularization. Angiographic follow-up was obtained in 18 patients (78%). Seven patients (38.8%) showed angiographic restenosis (> 50% luminal re-narrowing). No aneurysms or zones of ectasia were noted. CONCLUSION: This angiographic and clinical evaluation of the MHI Compassionate Use Registry data show the pullback technique to be safe from both a dosimetric and clinical point of view.

Beta Particles↗
PubMed2000

Optimization of radiosurgery treatment planning via mixed integer programming.

An automated optimization algorithm based on mixed integer programming techniques is presented for generating high-quality treatment plans for LINAC radiosurgery treatment. The physical planning in radiosurgery treatment involves selecting among a large collection of beams with different physical parameters an optimal beam configuration (geometries and intensities) to deliver the clinically prescribed radiation dose to the tumor volume while sparing the nearby critical structure and normal tissue. The proposed mixed integer programming models incorporate strict dose restrictions on tumor volume, and constraints on the desired number of beams, isocenters, couch angles, and gantry angles. The model seeks to deliver full prescription dose coverage and uniform radiation dose to the tumor volume while minimizing the excess radiation to the periphery normal tissue. In particular, it ensures that proximal normal tissues receive minimal dose via rapid dose fall-off. Preliminary numerical tests on a single patient case indicate that this approach can produce exceptionally high-quality plans in a fraction of the time required using the procedure currently employed by clinicians. The resulting plans provide highly uniform prescription dose to the tumor volume while drastically reducing the irradiation received by the proximal critical normal tissue.

Aged↗
PubMed1999

Radiation therapy to prevent coronary artery restenosis.

The problem of restenosis after coronary angioplasty remains a major limiting factor of the procedure. Intracoronary stenting has led to a modest reduction in the frequency of this event. In the early 1990s, the effectiveness of ionizing radiation combined with balloon angioplasty and stenting was first convincingly demonstrated in animal models of restenosis. Small feasibility studies and two randomized trials have, in general, supported the promise of these initial preclinical studies in the prevention of restenosis. Much remains to be learned about the application of radiation for this therapy. This article reviews the current status of preclinical and clinical investigation of this therapy.

Angioplasty, Balloon, Coronary↗
PubMed1999

Intravascular brachytherapy physics: report of the AAPM Radiation Therapy Committee Task Group no. 60. American Association of Physicists in Medicine.

Recent preclinical and clinical studies indicate that irradiation using ionizing radiation in the dose range of 15 to 30 Gy may reduce the occurrence of restenosis in patients who have undergone an angioplasty. Several delivery systems of intravascular brachytherapy have been developed to deliver radiation doses in this range with minimal normal tissue toxicity. In late 1995 the American Association of Physicists in Medicine (AAPM) formed a task group to investigate these issues and to report the current state of the art of intravascular brachytherapy physics. The report of this task group is presented here.

Angioplasty, Balloon, Coronary↗
PubMed1999

Significance of fatty acids in pregnancy-induced immunosuppression.

Pregnancy can exert suppressive effects on chronic inflammatory conditions. We have previously demonstrated a depression in polymorphonuclear leukocyte (PMN) respiratory burst during pregnancy which could explain this amelioration. To elucidate the biochemical mechanism, we have examined PMN phospholipase A2 (PLA2) activity and its relationship to cellular and circulating fatty acids in pregnant women (30 to 34 weeks) and nonpregnant controls. PMN PLA2 activity was determined by arachidonic acid (AA) and leukotriene B4 (LTB4) release, respiratory burst activity was determined by lucigenin-enhanced chemiluminescence, and total serum and PMN fatty acid levels were determined by gas-liquid chromatography. AA release was significantly reduced for pregnancy PMNs in response to N-formyl-met-leu-phe (fMLP) under unprimed and tumor necrosis factor alpha (TNF-alpha)- or interleukin 8-primed conditions. Similarly, LTB4 liberation was significantly reduced in response to fMLP and phorbol myristate acetate in unprimed and TNF-alpha-primed pregnancy PMNs. All major fatty acid classes were altered in the pregnant state. Of these differences in PMNs, oleic acid and alpha-linolenic acid showed a significant increase (13 and 26%, respectively) and stearic acid and AA showed a significant decrease (8 and 30%, respectively). The stearic acid, oleic acid, and AA compositions of all cells analyzed correlated with their corresponding changes in serum fatty acid levels. Crossover serum incubations modified both fatty acid profiles and the PMN respiratory burst accordingly, while individual fatty acid incorporation studies highlighted the importance of polyunsaturated fatty acids for NADPH oxidase efficiency. These findings indicate that the attenuation of PMN function in pregnancy may originate from a reduction in the available pool of cellular fatty acids. Furthermore, this reduction arises as a direct result of a pregnancy-induced shift in circulating fatty acids from polyunsaturated to monounsaturated forms.

Adolescent↗
PubMed1997

Stereotactic radiosurgery of malignant and benign intracranial lesions utilizing a patient rotator.

This study examines the characteristics of the patient groups, treatment parameters, and results of therapy for 126 intracranial lesions treated with stereotactic radiosurgery utilizing a "patient rotator" and a linear accelerator. A retrospective review was conducted and data on 122 patients (21 patients with arteriovenous malformations-AVMs, 40 patients with 41 metastatic tumors, 24 patients with malignant gliomas and 37 patients with other benign lesions) were analyzed. Clinical and radiographic response was obtained from chart review and/or telephone follow-up. The average follow-up was 12.1, 13.0, 5.7, and 23.1 months in patients with AVMs, malignant gliomas, metastases, and other lesions, respectively. Median survival times (MST) of the metastatic and glioma group were 9 and 38 months, respectively. Complete or partial radiographic response at follow-up was seen in 62.5% of AVM patients, 33.3% of patients with metastases, 11.8% of patients with malignant gliomas, and 19.3% of patients with other lesions. (1) Local control of brain metastases and benign intracranial lesions can be obtained with single dose stereotactic radiosurgery. (2) The MST and local control rate for metastatic disease obtained are comparable with those in the literature. (3) The patient rotator method for stereotactic radiosurgery is an effective tool for treating selected intracranial lesions.

Adult↗
PubMed1996

High dose cyclophosphamide, fractionated total body irradiation with involved field irradiation and autologous bone marrow transplantation in malignant lymphoma.

The objective of this clinical trial was to determine if radiation to areas of recurrence or bulky disease prior to total body irradiation (TBI) and chemotherapy followed by autologous bone marrow transplantation (ABMT) altered the site of relapse and/or prolonged survival. Forty-eight patients with recurrent or refractory malignant lymphoma were treated with high-dose cyclophosphamide and fractionated TBI followed by ABMT. Thirty-four patients were eligible to receive involved field radiation therapy (IF-RT) to sites of recurrence or bulky disease. The overall response rate in 46 evaluable patients was 89% with 33 complete remissions (CR) and 8 partial remissions (PR). In a multivariant analysis increasing LDH, decreased serum albumin, older age, and lack of sensitivity to prior chemotherapy were associated with poorer survival. There were 10 deaths due to treatment related complications, 8 died of pulmonary complications of whom 6 were in CR. Of 11 who had received IF-RT and subsequently relapsed, 4 recurred in or adjacent to the involved field. We conclude that intensive chemo-radiotherapy proved to be an effective salvage therapy for patients with recurrent malignant lymphoma, resulting in a projected actuarial 33% DFS at 5 years, but was associated with a high transplant-related mortality.

Adolescent↗
PubMed1993

Response to neoadjuvant chemotherapy in children with pineoblastoma.

BACKGROUND: The outlook of children with pineoblastoma treated with radiation therapy alone is extremely poor, but neoadjuvant chemotherapy has been tried only in a few cases of this rare childhood brain tumor with poor prognosis. METHODS: Three consecutive children 3 to 7 years of age received neoadjuvant chemotherapy consisting of etoposide 100 mg/m2 days 1 to 3, cisplatin 100 mg/m2 day 1, and vincristine 1.5 mg/m2 day 1, repeated every 4 weeks. After four courses of chemotherapy, patients underwent craniospinal irradiation. The radiation doses to the primary site ranged from 5040 to 5440 cGy and craniospinal axis radiation dose was 2520 to 3060 cGy. RESULTS: After chemotherapy, mild myelosuppression occurred in all three and mild to moderate bilateral high-frequency sensorineural hearing loss occurred in two of the three patients. One patient remains in near complete resolution of the tumor at 2 years after diagnosis and another remains in CR for 5 years. One patient achieved PR for 5 months but eventually died of progressive tumor. CONCLUSIONS: This study suggests that the neoadjuvant chemotherapy as used here is effective and has acceptable toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Childhood intracranial meningiomas after high-dose irradiation.

BACKGROUND: Irradiation, either alone or in association with other factors, is thought to play a role in the causation of intracranial meningioma. METHODS: The authors report two 15-year-old patients with convexity meningiomas as a result of high-dose irradiation received at a young age and review the English language literature reports of 13 pediatric patients with meningiomas after high-dose irradiation. The clinical characteristics of the 15 patients are presented. RESULTS: There were nine girls and six boys. The mean age at the time of irradiation was 2.5 years (2 months-9 years), and the mean age at diagnosis of meningioma was 13 years (5-15.5 years). The mean radiation dose was 4154 cGy (1500-8000 cGy). In 11 of the 15 patients, the meningioma was located in the calvarial area. Only 1 of 15 had multiple tumors, and only two of the tumors were clearly malignant at diagnosis. In ten patients, gross total resection was recorded, and two patients underwent subtotal resection. Three died of recurrent/disseminated meningiomas. CONCLUSIONS: This study suggests that meningiomas after high-dose radiation in children are mostly calvarial in location, rarely multiple, mostly benign in histologic type, and that complete removal is possible in most patients. The age at the time of radiation is young (mean age, 2.5 years) and the latent period is short (mean, 10.8 years). Although the clinical course of radiation-induced meningiomas in childhood generally is benign, high doses of radiation at a young age are to be avoided, and other means of therapy should be used if possible.

Astrocytoma↗
PubMed1991

Bone marrow transplant retinopathy.

Five of eight patients (62%) who survived at least six months after autologous or allogeneic bone marrow transplantation for acute leukemia developed occlusive microvascular retinopathy. Treatable retinal microangiopathy included a high incidence (80%) of clinically significant macular edema and one case of proliferative retinopathy with subhyaloid hemorrhage. The bone marrow transplant protocol required high-dose cytarabine hydrochloride and 1,200 cGy of total body irradiation. The development of radiation retinopathy after such low doses of teletherapy suggests that high-dose chemotherapy may increase the susceptibility for the development of retinopathy at otherwise safe radiation doses.

Adolescent↗
PubMed1991

Hyperfractionated radiation therapy in brain stem tumors. Results of treatment at the 7020 cGy dose level of Pediatric Oncology Group study #8495.

Between May 1986 and February 1988, 57 patients were accrued to the second dose level of a Phase I/II Pediatric Oncology Group (POG) study exploring the use of hyperfractionated radiation therapy (HRT) in children with high-risk brain stem tumors. Local fields were treated with fraction sizes of 117 cGy given twice daily, with a minimum interfraction interval of 6 hours, to a total dose of 7020 cGy in 60 fractions over 6 weeks. Information regarding clinical status during HRT was available for 55 patients (44 [80%] improved, 6 remained stable, and 5 deteriorated). Results of initial and follow-up computed tomography (CT) scan and/or magnetic resonance imaging (MRI) were available for review for 52 patients. One patient had a complete response (CR) to treatment, 3 had a partial response (PR) (more than 50% response), and 40 remained stable, for a total response rate (CR + PR + stable) of 77%. Median time to disease progression was 6 months. Median survival time was 10 months. Survival rate was 39.6% (standard error [SE] = 6.6%) at 1 year and 23% (SE = 5.8%) at 2 years. Complications of treatment included an enhanced skin reaction in six patients and otitis media and/or externa in nine. One patient bled into tumor shortly after completion of HRT, and three had intralesional necrosis. Five patients continued taking steroids for protracted periods in the face of improved clinical and/or radiologic findings. Complications related to the use of steroids included opportunistic infections, impaired glucose tolerance, hypertension, osteoporosis, and significant mood changes. In no patient was there evidence of any late injury attributable to HRT. When compared with results of treatment with HRT at a lower dose level (6600 cGy), there appears to be a trend toward improved survival at 7020 cGy despite a less favorable patient population at the higher dose level. A second dose escalation to 7560 cGy in 60 fractions over 6 weeks has been implemented as planned.

Adolescent↗
PubMed1990

Ophthalmological and other toxicities related to cytosine arabinoside and total body irradiation as preparative regimen for bone marrow transplantation.

Cytosine arabinoside, 3 g/m2, every 12 h for 6 days, followed by fractionated total body irradiation, 200 cGy twice daily for 3 days, was administered to 39 adult patients undergoing bone marrow transplantation. Allogeneic transplant patients received cyclosporin and methotrexate for prophylaxis of graft-versus-host disease. There were 21 autologous transplants (16 with acute leukemia, four with an advanced stage of chronic myelocytic leukemia, and one with lymphoma) and 18 allogeneic transplants (14 with acute leukemia, two with an advanced stage of chronic myelocytic leukemia and two with myelodysplastic syndrome). Toxicities were compared between the two groups. There was a significantly greater degree and duration of mucositis and a greater frequency of radiation-type retinopathy developing in the allogeneic group, predominantly in those having had radiation for prophylaxis or treatment of central nervous system leukemia. Seven of 11 acute leukemic patients who received autologous transplants in remission survive. Two of seven acute leukemias who received allogeneic transplants while in remission survive. Although the increased morbidity, retinitis and mucositis, observed in the allogeneic group indicates that this regimen when combined with methotrexate and cyclosporin is too toxic, the results in autologous transplantation in acute leukemia in remission are encouraging.

Bone Marrow Transplantation↗
PubMed1989

Adjuvant chemotherapy for advanced nasopharyngeal carcinoma in childhood.

Seven children with advanced nasopharyngeal carcinoma younger than 20 years of age diagnosed between 1975 and 1986 (inclusive) were treated with a uniform adjuvant chemotherapy regimen, which consisted of vincristine (1.5 mg/m2; day 1), doxorubicin (45 mg/m2; day 1), 5-fluorouracil (8 mg/kg; days 1 through 5), and cyclophosphamide (7 mg/kg; days 1 through 5). This combination chemotherapy was given for 12 to 24 months after completion of radiation therapy. The radiation doses to the primary sites ranged from 6000 cGy to a maximum of 6800 cGy. The radiation doses for neck prophylaxis ranged from 4500 cGy to a total of 5000 cGy. Involved sites were irradiated to at least an additional boost of 1000 cGy. One patient had an external dose 6000 cGy to the primary site boosted with brachytherapy of 3000 cGy at the surface of an ovoid. After chemotherapy myelosuppression occurred in all patients and was tolerable. All seven patients are surviving, six disease-free, for 22 months to 12 years (median, 4 years). This study suggests that the combination of radiation therapy and chemotherapy as used here has acceptable toxicity and is effective and further suggests that children with nasopharyngeal carcinoma, even in its advanced stage at diagnosis, may be curable.

Adolescent↗