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2.
Radiat Environ Biophys ; 48(3): 295-310, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19521713

ABSTRACT

The results of electron paramagnetic resonance (EPR) measurements in irradiated fingernails are presented. In total, 83 samples of different fingernails were studied. Five different groups of samples were selected based on the collection time of fingernail samples, their level of mechanical stress, and the number and size of clippings: (1) recently (<24 h) cut, irradiated and measured with EPR without any treatment of samples, and with rigorous control of size and number of clippings (stressed-fresh, controlled); (2) recently (<24 h) cut, irradiated and measured with EPR after application of a special treatment (10 min of water soaking, 5 min of drying time) to reduce the mechanical stress caused by cutting the samples, and with rigorous control of size and number of clippings (unstressed-fresh, controlled); (3) previously (>24 h) cut, stored at room temperature, additionally cut into small pieces immediately prior to study, irradiated and measured with EPR without any treatment of samples, and with rigorous control of size and number of clippings (stressed-old, controlled); (4) previously (>24 h) cut, stored at room temperature, additionally cut into small pieces immediately prior to the study, irradiated and measured with EPR after application of a special treatment to reduce mechanical stress caused by cut, and with rigorous control of size and number of clippings (unstressed-old, controlled); and (5) recently (<24 h) cut, irradiated and measured with EPR after application of a special treatment to reduce the mechanical stress caused by cut, and without rigorous control of size and number of clippings (unstressed-fresh, uncontrolled). Except for the fifth selected group, variability of the dose dependence inside all groups was found to be not statistically significant, although the variability among the different groups was significant. Comparison of the mean dose dependences obtained for each group allowed selection of key factors responsible for radiation sensitivity (dose response per unit of mass and dose) and the shape of dose dependence in fingernails. The major factor responsible for radiation sensitivity of fingernails was identified as their water content, which can affect radiation sensitivity up to 35%. The major factor responsible for the shape of the radiation sensitivity was identified as the mechanical stress. At a significant level of mechanical stress, the shape of the dose dependence is linear in the studied dose range (<20 Gy), and in lesser-stressed samples it is of an exponential growth including saturation, which depends on the degree of mechanical stress. In view of the findings, recommendations are discussed and presented for the appropriate protocol for EPR dose measurements in fingernails.


Subject(s)
Nails/radiation effects , Adult , Dose-Response Relationship, Radiation , Electron Spin Resonance Spectroscopy , Humans , Immersion , Middle Aged , Radiation Dosage , Stress, Mechanical , Temperature , Time Factors , Water , Young Adult
3.
Radiat Environ Biophys ; 47(4): 515-26, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18584193

ABSTRACT

The most significant problem of electron paramagnetic resonance (EPR) fingernail dosimetry is the presence of two signals of non-radiation origin that overlap the radiation-induced signal (RIS), making it almost impossible to perform dose measurements below 5 Gy. Historically, these two non-radiation components were named mechanically induced signal (MIS) and background signal (BKS). In order to investigate them in detail, three different methods of MIS and BKS mutual isolation have been developed and implemented. After applying these methods, it is shown here that fingernail tissue, after cut, can be modeled as a deformed sponge, where the MIS and BKS are associated with the stress from elastic and plastic deformations, respectively. A sponge has a unique mechanism of mechanical stress absorption, which is necessary for fingernails in order to perform its everyday function of protecting the fingertips from hits and trauma. Like a sponge, fingernails are also known to be an effective water absorber. When a sponge is saturated with water, it tends to restore to its original shape, and when it loses water, it becomes deformed again. The same happens to fingernail tissue. It is proposed that the MIS and BKS signals of mechanical origin be named MIS1 and MIS2 for MISs 1 and 2, respectively. Our suggested interpretation of the mechanical deformation in fingernails gives also a way to distinguish between the MIS and RIS. The results obtained show that the MIS in irradiated fingernails can be almost completely eliminated without a significant change to the RIS by soaking the sample for 10 min in water. The proposed method to measure porosity (the fraction of void space in spongy material) of the fingernails gave values of 0.46-0.48 for three of the studied samples. Existing results of fingernail dosimetry have been obtained on mechanically stressed samples and are not related to the "real" in vivo dosimetric properties of fingernails. A preliminary study of these properties of pre-soaked (unstressed) fingernails has demonstrated their significant difference from fingernails stressed by cut. They show a higher stability signal, a less intensive non-radiation component, and a nonlinear dose dependence. The findings in this study set the stage for understanding fingernail EPR dosimetry and doing in vivo measurements in the future.


Subject(s)
Biological Assay/methods , Biomimetic Materials/chemistry , Electron Spin Resonance Spectroscopy/methods , Nails/chemistry , Radiometry/methods , Humans , Radiation Dosage , Relative Biological Effectiveness , Reproducibility of Results , Sensitivity and Specificity
4.
J Virol ; 78(4): 2121-30, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14747577

ABSTRACT

Newborn rhesus macaques were infected with two chimeric simian-human immunodeficiency virus (SHIV) strains which contain unique human immunodeficiency virus type 1 (HIV-1) env genes and exhibit distinct phenotypes. Infection with either the CCR5-specific SHIV(SF162P3) or the CXCR4-utilizing SHIV(SF33A) resulted in clinical manifestations consistent with simian AIDS. Most prominent in this study was the detection of severe thymic involution in all SHIV(SF33A)-infected infants, which is very similar to HIV-1-induced thymic dysfunction in children who exhibit a rapid pattern of disease progression. In contrast, SHIV(SF162P3) induced only a minor disruption in thymic morphology. Consistent with the distribution of the coreceptors CXCR4 and CCR5 within the thymus, the expression of SHIV(SF162P3) was restricted to the thymic medulla, whereas SHIV(SF33A) was preferentially detected in the cortex. This dichotomy of tissue tropism is similar to the differential tropism of HIV-1 isolates observed in the reconstituted human thymus in SCID-hu mice. Accordingly, our results show that the SHIV-monkey model can be used for the molecular dissection of cell and tissue tropisms controlled by the HIV-1 env gene and for the analysis of mechanisms of viral immunopathogenesis in AIDS. Furthermore, these findings could help explain the rapid progression of disease observed in some HIV-1-infected children.


Subject(s)
HIV-1/pathogenicity , Receptors, CCR5/metabolism , Receptors, CXCR4/metabolism , Simian Acquired Immunodeficiency Syndrome/physiopathology , Simian Immunodeficiency Virus/pathogenicity , Thymus Gland/pathology , Animals , Animals, Newborn , HIV-1/genetics , HIV-1/metabolism , Macaca mulatta , Recombination, Genetic , Simian Acquired Immunodeficiency Syndrome/pathology , Simian Acquired Immunodeficiency Syndrome/virology , Simian Immunodeficiency Virus/genetics , Simian Immunodeficiency Virus/metabolism , Thymus Gland/virology
5.
Otolaryngol Head Neck Surg ; 122(2): 272-6, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10652406

ABSTRACT

This is an 8-year follow-up of a group of 214 patients who underwent surgical insertion of titanium implants in the mastoid process for the retention of bone-anchored hearing aids and auricular prostheses. The skin reactions around the implants and the various factors dealing with implant loss were evaluated. The number of patients who never had any episode of adverse skin reactions during the 8-year period is 70% and is about the same as previously reported. The frequency and degree of adverse skin reactions were noted to be decreasing with time. The young age group had the highest incidence of adverse skin reactions, and this high frequency is consistent with results of earlier reports. None of the remaining group of patients (30%) who had 1 or more episodes of adverse skin reactions lost their implants because of this problem; most implant losses were primarily the result of loss of integration. The probability of losing an implant because of adverse skin reactions is quite low; however, these skin reactions, if left untreated, may eventually lead to implant loss or withdrawal.


Subject(s)
Ear, External/surgery , Foreign-Body Reaction/pathology , Hearing Aids , Mastoid/surgery , Prostheses and Implants/adverse effects , Skin/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Titanium
6.
Virology ; 265(2): 235-51, 1999 Dec 20.
Article in English | MEDLINE | ID: mdl-10600596

ABSTRACT

The simian immunodeficiency virus (SIV) nef gene is an important determinant of viral load and acquired immunodeficiency syndrome (AIDS) in macaques. A role(s) for the HIV-1 nef gene in infection and pathogenesis was investigated by constructing recombinant viruses in which the nef gene of the pathogenic molecular clone SIVmac239 nef was replaced with either HIV-1sf2nef or HIV-1sf33nef. These chimeras, designated SHIV-2nef and SHIV-33nef, expressed HIV-1 Nef protein and replicated efficiently in cultures of rhesus macaque lymphoid cells. In two SHIV-2nef-infected juvenile rhesus macaques and in one of two SHIV-33nef-infected juvenile macaques, virus loads remained at low levels in both peripheral blood and lymph nodes in acute and chronic phases of infection (for >83 weeks). In striking contrast, the second SHIV-33nef-infected macaque showed high virus loads during the chronic stage of infection (after 24 weeks). CD4+ T-cell numbers declined dramatically in this latter animal, which developed simian AIDS (SAIDS) at 47-53 weeks after inoculation; virus was recovered at necropsy at 53 weeks and designated SHIV-33Anef. Sequence analysis of the HIV-1sf33 nef gene in SHIV-33Anef revealed four consistent amino acid changes acquired during passage in vivo. Interestingly, one of these consensus mutations generated a tyr-x-x-leu (Y-X-X-L) motif in the HIV-1sf33 Nef protein. This motif is characteristic of certain endocytic targeting sequences and also resembles a src-homology region-2 (SH-2) motif found in many cellular signaling proteins. Four additional macaques infected with SHIV-33Anef contained high virus loads, and three of these animals progressed to fatal SAIDS. Several of the consensus amino acid changes in Nef, including Y-X-X-L motif, were retained in these recipient animals exhibiting high virus load and disease. In summary, these findings indicate that the SHIV-33Anef chimera is pathogenic in rhesus macaques and that this approach, i.e., construction of chimeric viruses, will be important for analyzing the function(s) of HIV-1 nef genes in immunodeficiency in vivo, testing antiviral therapies aimed at inhibiting AIDS, and investigating adaptation of this HIV-1 accessory gene to the macaque host.


Subject(s)
Gene Products, nef/physiology , HIV-1 , Simian Acquired Immunodeficiency Syndrome/virology , Simian Immunodeficiency Virus/pathogenicity , Amino Acid Sequence , Animals , Cell Line , Gene Products, nef/genetics , Humans , Macaca mulatta , Molecular Sequence Data , Recombination, Genetic , Sequence Homology, Amino Acid , Simian Immunodeficiency Virus/genetics , nef Gene Products, Human Immunodeficiency Virus
7.
J Virol ; 72(5): 4237-42, 1998 May.
Article in English | MEDLINE | ID: mdl-9557713

ABSTRACT

Degenerate PCR primers which amplify a conserved region of the DNA polymerase genes of the herpesvirus family were used to provide sequence evidence for a new bovine herpesvirus in bovine B-lymphoma cells and peripheral blood mononuclear cells (PBMC). The sequence of the resultant amplicon was found to be distinct from those of known herpesvirus isolates. Alignment of amino acid sequences demonstrated 70% identity with ovine herpesvirus 2, 69% with alcelaphine herpesvirus 1, 65% with bovine herpesvirus 4, and 42% with bovine herpesvirus 1. Phylogenetic analysis placed this putative virus within the tumorigenic Gammaherpesvirinae subfamily, and it is tentatively identified as bovine lymphotropic herpesvirus. This novel agent was expressed in vitro from infected PBMC, and cell-free supernatants were used to transfer infection to a bovine B-cell line, BL3. Analysis, with specific PCR primers, of DNA from bovine PBMC and lymphoma cells identified infection in blood of 91% of adult animals (n = 101), 63% of lymphomas (n = 32), and 38% of juveniles (n = 13). Of the adults, herpesvirus infection was present in 94% of animals that were seropositive for bovine leukemia virus (BLV) (n = 63) and in 87% of BLV-seronegative animals (n = 38). Of the seropositive group, 17 animals exhibited persistent lymphocytosis, and 100% of these were herpesvirus positive by PCR. A role for bovine lymphotropic herpesvirus as a cofactor in BLV pathogenesis is considered.


Subject(s)
Cattle Diseases/virology , Gammaherpesvirinae/isolation & purification , Lymphoma, B-Cell/veterinary , Amino Acid Sequence , Animals , Base Sequence , Cattle , Cell Line , Cell-Free System , Consensus Sequence , Culture Media , DNA, Viral , DNA-Directed DNA Polymerase/genetics , Gammaherpesvirinae/classification , Gammaherpesvirinae/enzymology , Gammaherpesvirinae/genetics , Genes, Viral , Humans , Leukocytes, Mononuclear/virology , Lymphocytosis/virology , Lymphoma, B-Cell/virology , Molecular Sequence Data , Phylogeny , Polymerase Chain Reaction , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Sequence Homology, Nucleic Acid , Sheep
8.
Virology ; 242(1): 184-92, 1998 Mar 01.
Article in English | MEDLINE | ID: mdl-9501056

ABSTRACT

To further investigate the molecular basis underlying the dysregulation of B cell homeostasis associated with bovine leukemia virus disease progression in cattle, bovine bax was cDNA cloned and sequenced. The predicted amino acid sequence of bovine Bax revealed a 192-amino-acid protein having extensive identity with the human (97%), murine (93%), and rat (94%) homologues. Because the ratio of Bcl-2 to Bax is believed to predetermine the susceptibility to a given apoptotic stimulus, the relative expression of the genes encoding these oncoproteins was evaluated in cattle naturally infected with BLV. In BLV-infected cattle an increase in the ratios of bcl-2/bax mRNA and protein expression correlated with advancing stages of disease. These findings suggest that in addition to the maintenance of BLV-associated hematopoietic malignancies, the reciprocal expression of Bcl-2/Bax may modulate the induction of B cell expansion typical of BLV disease progression.


Subject(s)
Enzootic Bovine Leukosis/virology , Leukemia Virus, Bovine/pathogenicity , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Proto-Oncogene Proteins/biosynthesis , Amino Acid Sequence , Animals , Base Sequence , Cattle , Cloning, Molecular , DNA Primers , Enzootic Bovine Leukosis/physiopathology , Female , Humans , Molecular Sequence Data , Oligonucleotide Probes , Proto-Oncogene Proteins/chemistry , Proto-Oncogene Proteins c-bcl-2/chemistry , Rats , Recombinant Proteins/biosynthesis , Recombinant Proteins/chemistry , Sequence Alignment , Sequence Homology, Amino Acid , bcl-2-Associated X Protein
9.
J Virol ; 70(8): 4961-5, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8764001

ABSTRACT

The correlation between bovine leukemia virus (BLV) unintegrated DNA, viral expression, and stage of disease was determined in cattle naturally infected with BLV. The concomitant presence of unintegrated BLV DNA with viral transcriptional activity was observed in 53% (18 of 34) of hematologically normal, BLV-seropositive cattle and in 100% (10 of 10) of BLV-seropositive cattle with the preneoplastic syndrome persistent lymphocytosis. In vitro studies suggested that accumulation of unintegrated BLV DNA resulted from a process of reinfection rather than intracellular reverse transcription of newly synthesized BLV RNA. Interestingly, unintegrated BLV DNA was not detected in tumor cells from cattle with BLV-associated lymphocytic leukemia/malignant lymphoma despite viral transcriptional activity in 100% (eight of eight) of these cattle. Thus, the presence of unintegrated BLV DNA differentiated nonneoplastic from neoplastic conditions in BLV-infected cattle. These results demonstrate that unintegrated viral DNA serves as a marker of disease progression in BLV-infected cattle but is not necessarily associated with induction or maintenance of the neoplastic state.


Subject(s)
DNA, Viral/analysis , Enzootic Bovine Leukosis/genetics , Leukemia Virus, Bovine/genetics , Virus Integration/genetics , Animals , Biomarkers/analysis , Cattle , Enzootic Bovine Leukosis/virology , Female
11.
Neurosurgery ; 32(3): 464-7; discussion 467, 1993 Mar.
Article in English | MEDLINE | ID: mdl-8455775

ABSTRACT

The authors report the clinical course and surgical technique used to treat a patient with a high-grade stenosis of the proximal middle cerebral artery that had caused a previous infarction and threatened the remaining dominant hemisphere. Trapping of the involved middle cerebral artery segment allowed direct exposure for excision of the atheromatous plaque and subsequent closure of the arteriotomy. Intraoperative angiography confirmed the reestablishment of flow. The patient made an uneventful postoperative recovery. Direct middle cerebral artery endarterectomy has the advantage of potentially reestablishing flow to lenticulostriate branches. The technique may also avoid the problem of occlusion at the site of maximum stenosis that can be caused by the use of an extra/intracranial bypass graft. Middle cerebral artery endarterectomy is a potentially valuable technique that deserves further investigation.


Subject(s)
Cerebral Infarction/surgery , Endarterectomy , Cerebral Angiography , Cerebral Infarction/diagnostic imaging , Humans , Intracranial Arteriosclerosis/diagnostic imaging , Intracranial Arteriosclerosis/surgery , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Tomography, X-Ray Computed
12.
Phys Ther ; 73(2): 117-22, 1993 Feb.
Article in English | MEDLINE | ID: mdl-8421717

ABSTRACT

BACKGROUND AND PURPOSE: The purposes of this study were to compare test-retest reliability of measurements obtained by the use of a photographic method and those obtained by the use of a transparency method and to compare wound surface area (WSA) measurements obtained by these two methods. SUBJECTS: Twenty inpatients (18 male, 2 female), aged 31 +/- 16 years (mean +/- SD), participated in the study. METHODS: Tracings of ulcer borders generated by the photographic and transparency methods were digitized to obtain WSA measurements. To assess intrarater reliability for each method, 5 ulcers were measured on two occasions. The magnitude of WSA measurements obtained by the photographic and transparency methods was compared in 22 ulcers measured on one occasion and in 16 ulcers measured at 5-day intervals for 20 days. RESULTS: Intraclass correlation coefficients (ICCs) were high (ICC = .99) for each method, indicating reliability of measurements. The WSA measurements did not differ between photographic and transparency methods, either at one occasion or over a 20-day period. CONCLUSION AND DISCUSSION: We concluded that the photographic and transparency methods, as applied in this study of ulcers, provided equivalently reliable measurements and that WSA measurements obtained by the two methods were equivalent. The transparency method was more economical than the photographic method in terms of time and equipment requirements.


Subject(s)
Anthropometry/methods , Body Surface Area , Photography/standards , Pressure Ulcer/diagnosis , Adult , Analysis of Variance , Bias , Evaluation Studies as Topic , Female , Humans , Male , Observer Variation , Photography/economics , Photography/methods , Pressure Ulcer/classification , Pressure Ulcer/pathology , Reproducibility of Results , Severity of Illness Index
13.
Surg Neurol ; 38(5): 379-82, 1992 Nov.
Article in English | MEDLINE | ID: mdl-1485215

ABSTRACT

The authors discuss the choice of the transoral-transclival approach for the repair of a lower basilar artery aneurysm in a 32-year-old sickle-cell patient. Efficiency of approach and minimization of damage to vital structures support the use of this technique. The risks of cerebrospinal fluid fistula and meningitis are considered. One year after operation, the patient is neurologically intact.


Subject(s)
Basilar Artery/surgery , Intracranial Aneurysm/surgery , Adult , Basilar Artery/pathology , Constriction , Cranial Fossa, Posterior , Humans , Intracranial Aneurysm/pathology , Male , Mouth , Postoperative Complications
14.
Neurosurgery ; 31(3): 597-601; discussion 601-2, 1992 Sep.
Article in English | MEDLINE | ID: mdl-1407442

ABSTRACT

A new approach to the basilar apex in a patient with a megadolichobasilar anomaly and an abnormally rostral basilar apex aneurysm is described. The details of the surgical approach and the advantages and limitations of this transcallosal, interseptal approach are described.


Subject(s)
Basilar Artery , Intracranial Aneurysm/surgery , Adult , Basilar Artery/surgery , Cerebral Angiography , Cerebral Ventricles , Corpus Callosum , Humans , Intracranial Aneurysm/diagnostic imaging , Male , Tomography, X-Ray Computed
15.
Bol Med Hosp Infant Mex ; 49(7): 441-8, 1992 Jul.
Article in Spanish | MEDLINE | ID: mdl-1418652

ABSTRACT

We report two male adolescents who developed septic thrombosis of the cavernous sinuses after manipulation of a furuncle on the nasal dorsum. We noted in both patients, besides the clinical findings of a generalized infectious process, palpebral edema, proptosis, ptosis, altered pupillary reactivity and bilateral III, IV and VI nerve palsies, as well as dysfunction of the ophthalmic branch of the fifth cranial nerve. One of the patients also had bacterial meningitis. Their cerebral angiograms demonstrated narrowing of the intracavernous portion of both internal carotid arteries. They improved with the antimicrobial treatment, but were left with ptosis and ocular palsies as sequelae. The adequate management of facial furuncle to prevent such a serious complication is emphasized.


Subject(s)
Cavernous Sinus , Furunculosis/complications , Sinus Thrombosis, Intracranial/microbiology , Adolescent , Humans , Male
16.
Bol Med Hosp Infant Mex ; 49(6): 384-7, 1992 Jun.
Article in Spanish | MEDLINE | ID: mdl-1632912

ABSTRACT

We report the case of a 4-year-old female who developed an extensive cerebral infarction after trauma to the right peritonsillar area with a spoon. Blunt injury to the intima of the interna carotid artery promotes thrombus formation or clot embolization which results in an ischemic cerebrovascular event. We emphasize the need to prevent this rare complication of intraoral trauma in childhood.


Subject(s)
Carotid Artery Injuries , Cerebral Infarction/etiology , Palatine Tonsil/injuries , Wounds, Nonpenetrating/complications , Accidental Falls , Cerebral Infarction/diagnosis , Child, Preschool , Electroencephalography , Emergencies , Female , Hemiplegia/diagnosis , Hemiplegia/etiology , Humans , Wounds, Nonpenetrating/diagnosis
17.
Surg Neurol ; 33(3): 185-91, 1990 Mar.
Article in English | MEDLINE | ID: mdl-2180096

ABSTRACT

The lower portion of the basilar artery is a site of significant disease, both aneurysmal and stenotic, but has been considered inaccessible via traditional surgical approaches. A baboon model was used to evaluate the feasibility of a direct surgical reconstruction via a transoral-transclival approach, utilizing temporary occlusion of the basilar artery. An arteriotomy was performed and either repaired primarily or a venous patch graft was sutured in place. All animals survived the surgery; one suffered fatal postoperative upper airway obstruction, but the other four were neurologically intact at the time of death. Patency at the site of repair was confirmed both angiographically and histologically. We conclude that temporary clamping in conjunction with direct reconstruction of the basilar artery is feasible in this primate model. Future studies will focus on further applications of this technique.


Subject(s)
Basilar Artery/surgery , Intracranial Aneurysm/surgery , Vertebrobasilar Insufficiency/surgery , Animals , Brain Ischemia/physiopathology , Brain Stem/physiopathology , Disease Models, Animal , Male , Papio , Pilot Projects , Suture Techniques
18.
Neurosurgery ; 26(3): 528-33, 1990 Mar.
Article in English | MEDLINE | ID: mdl-2181338

ABSTRACT

A case of a 47-year-old man with weakness secondary to ossification of the posterior longitudinal ligament is presented. During removal of the ossified ligament, the patient's dominant right vertebral artery was injured. Although the bleeding from this artery was controlled intraoperatively, the patient developed an expanding cervical hematoma on the 3rd postoperative day. An angiogram demonstrated a large pseudoaneurysm of the right vertebral artery. The patient was taken back to the operating room where the cervical hematoma was removed, and direct repair of the pseudoaneurysm of the vertebral artery was performed. The previously reported cases of pseudoaneurysms of the extracranial vertebral artery are reviewed. We advocate the use of direct vascular repair as the treatment of choice in these lesions.


Subject(s)
Hematoma/surgery , Vascular Diseases/surgery , Vascular Surgical Procedures/methods , Vertebral Artery/surgery , Hematoma/etiology , Humans , Male , Middle Aged , Vascular Diseases/etiology , Vertebral Artery/injuries
20.
J Clin Oncol ; 5(5): 783-9, 1987 May.
Article in English | MEDLINE | ID: mdl-3553437

ABSTRACT

Employment of postoperative brain irradiation in the initial management of high-grade malignant glial tumors has now become standard. The addition of conventional chemotherapy to irradiation has not significantly improved median survival beyond 1 year. We treated 25 consecutive patients (13 pilot patients and 12 protocol patients) with histologically confirmed unresectable grade 3 or 4 malignant gliomas with high-dose BCNU (carmustine) followed by autologous bone marrow transplantation and whole brain irradiation. Within 3 weeks of initial surgery, each patient had autologous bone marrow stored (median 2 X 10(8) nucleated cells/kg), and then received BCNU 1,050 mg/m2 intravenously (IV). Peripheral granulocytes recovered (greater than 500/microL) at a median of 19 days (range, 10 to 37 days), and platelets recovered (greater than 20,000/microL) at a median of 18 days (range, 13 to 40 days), following bone marrow infusion. Patients received 60 Gy whole brain irradiation when granulocytes were greater than 1,500/microL. Toxicity was well tolerated. Nausea occurred in 19 patients (76%); however, only eight patients (32%) experienced vomiting (mild in three, moderate in five). Eleven patients (44%) did not require empiric antibiotics, six of whom never developed an absolute granulocyte count less than 500/microL. Three patients with a poor performance status died early (one seizure with vomiting and asphyxiation; one, klebsiella urinary tract infection (UTI) with bacteremia; one, candidal pneumonia), and one additional patient who was performing well died of pulmonary hemorrhage. The 13 pilot patients have now been followed for a median of 23 months, with a significant survival advantage compared with the 52 consecutive historical control patients who received similar surgery and radiotherapy without high-dose BCNU (P = .037). The overall study group of 25 patients also has a significant survival advantage when compared with the same historical control group, with a projected median survival of 26 months (P = .007). This new approach using early postoperative intensive therapy consisting of high-dose BCNU, autologous bone marrow transplantation, and whole brain irradiation appears to significantly improve survival.


Subject(s)
Bone Marrow Transplantation , Brain Neoplasms/therapy , Carmustine/administration & dosage , Glioma/therapy , Adult , Brain Neoplasms/radiotherapy , Brain Neoplasms/surgery , Carmustine/adverse effects , Combined Modality Therapy , Female , Glioma/radiotherapy , Glioma/surgery , Humans , Male , Middle Aged , Nausea/chemically induced , Transplantation, Autologous
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