Biomedical subjects

A Olivi

Publications and source records attributed to A Olivi.

At least 19 recordsLinked to original sources

PubMed2006

Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells.

Transformed, oncogenic precursors, possessing both defining neural-stem-cell properties and the ability to initiate intracerebral tumours, have been identified in human brain cancers. Here we report that bone morphogenetic proteins (BMPs), amongst which BMP4 elicits the strongest effect, trigger a significant reduction in the stem-like, tumour-initiating precursors of human glioblastomas (GBMs). Transient in vitro exposure to BMP4 abolishes the capacity of transplanted GBM cells to establish intracerebral GBMs. Most importantly, in vivo delivery of BMP4 effectively blocks the tumour growth and associated mortality that occur in 100% of mice after intracerebral grafting of human GBM cells. We demonstrate that BMPs activate their cognate receptors (BMPRs) and trigger the Smad signalling cascade in cells isolated from human glioblastomas (GBMs). This is followed by a reduction in proliferation, and increased expression of markers of neural differentiation, with no effect on cell viability. The concomitant reduction in clonogenic ability, in the size of the CD133+ population and in the growth kinetics of GBM cells indicates that BMP4 reduces the tumour-initiating cell pool of GBMs. These findings show that the BMP-BMPR signalling system--which controls the activity of normal brain stem cells--may also act as a key inhibitory regulator of tumour-initiating, stem-like cells from GBMs and the results also identify BMP4 as a novel, non-cytotoxic therapeutic effector, which may be used to prevent growth and recurrence of GBMs in humans.

AC133 Antigen↗

PubMed2003

Visual and electrical evoked response recorded from subdural electrodes implanted above the visual cortex in normal dogs under two methods of anesthesia.

Sensitive methods are required to record electrical evoked potentials over the visual cortex to evaluate the efficacy and safety of a retinal prosthesis before it can be implanted on the retinal surface of patients afflicted by outer retinal diseases. This study was designed to examine subdural electrodes as a mean to evaluate cortical evoked potentials in response to light and electrical stimulation of the retina in three dogs under two methods of anesthesia-halothane and propofol. Results showed that subdural electrodes could be stabilized over the visual cortex for several (3-5) months, and that they were 6.95 times more sensitive than subdermal electrodes in recording cortical visual evoked potentials (VEPs) and 4.31 times more sensitive in recording cortical electrical evoked potentials under both methods of anesthesia. The waveforms' shape changed for each electrode in the subdural array during 6/6 (100%) and 20/38 (52%) multi-channel recording sessions under halothane and propofol, respectively. This change could point to a cortical retinotopic organization versus hierarchical organization of different cortical areas for a given retinal stimulus. In summary, subdural electrodes show promising results for recording visual and electrical evoked responses (EERs) and thus for evaluation of the retinal prosthesis.

Anesthesia↗

PubMed2003

Spinal meningioma causing diffuse leptomeningeal enhancement.

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Adult↗

PubMed2001

Cystic prostate metastases to the brain parenchyma: report of two cases and review of the literature.

Prostate carcinoma is among the leading causes of cancer death for American men. Intracranial metastases from prostatic adenocarcinoma are unusual, and cystic metastases are rare. Two cases of cystic intraparenchymal metastases from prostatic adenocarcinoma are reported. Our comprehensive literature review revealed that prostatic adenocarcinoma metastases are rarely diagnosed antemortem. If these lesions are detected early and treated with surgery and radiation therapy, survival time for patients with prostatic adenocarcinoma may be increased; however, given the rarity of these cases, routine CNS imaging of men with metastatic prostate cancer does not seem warranted.

Adenocarcinoma↗

PubMed2001

Reversible posterior leukoencephalopathy occurring during resection of a posterior fossa tumor: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Our goal was to present a clinically and radiographically documented case of reversible posterior leukoencephalopathy (RPL) that occurred during resection of a posterior fossa tumor. Although RPL has been previously described in multiple nonsurgical settings, we hope that this case description makes RPL more clinically and radiographically recognizable to neurosurgeons. CLINICAL PRESENTATION: RPL is the clinical syndrome of headaches, altered mental status, seizures, and visual loss, with radiographic findings of reversible parieto-occipital changes on cerebral computed tomographic and magnetic resonance imaging scans. It has been previously reported in the settings of malignant hypertension, renal disease, eclampsia, and immunosuppression. To our knowledge, the patient presented represents the first clinically and radiographically documented case of RPL occurring during resection of a posterior fossa tumor. The patient intraoperatively exhibited wide fluctuations in blood pressure and awoke with clinical and radiographic findings consistent with RPL. INTERVENTION: Aggressive intraoperative and postoperative management of the patient's blood pressure, supportive intensive care, rehabilitation, and close radiographic follow-up were performed. CONCLUSION: RPL can occur as a result of intraoperative variations in blood pressure, even among young, previously healthy individuals. With the aforementioned interventions, the patient experienced significant clinical and radiographic recovery.

Adult↗

PubMed2000

Paracrine delivery of IL-12 against intracranial 9L gliosarcoma in rats.

OBJECT: Interleukin-12 (IL- 12) has potential for the treatment of tumors because it can stimulate an antitumor immune response and possesses antiangiogenic properties. In the study reported here, the authors investigated the therapeutic role of locally delivered IL-12 in a malignant brain tumor model. METHODS: After genetically engineering 9L gliosarcoma cells to express IL-12 (9L-IL12 cells), the authors used these cells as a source of locally delivered cytokine. First, they investigated the behavior of these cells, which were implanted with the aid of stereotactic guidance into the rat brain, by using serial magnetic resonance imaging and histopathological examination. Second, they assessed the antitumor efficacy of proliferating, as well as nonproliferating (irradiated), 9L-IL12 cells by implanting these cells in animals challenged by wild-type 9L gliosarcoma (9Lwt) cells. The IL-12 expression in brain regions injected with 9L-IL12 was confirmed by reverse transcription-polymerase chain reaction. Last, the authors explored whether animals treated with 9L-IL12 cells developed an antitumor immunological memory by rechallenging the survivors with a second injection of 9Lwt cells. The authors demonstrated that local delivery of IL-12 into the rat brain by genetically engineered cells significantly prolongs survival time in animals challenged intracranially with a malignant glioma. CONCLUSIONS: These findings support continued efforts to refine local delivery systems of IL-12 in an attempt to bring this therapy to clinical trials.

Animals↗

PubMed2000

Synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome presenting as a primary calvarial lesion. Case report and review of the literature.

The synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a recently described, currently evolving clinical entity that groups together several idiopathic disorders of bone and skin formerly described under a variety of names. Among the spectrum of possible locations for the bone lesions, there is no previous report in the literature of primary involvement of the skull vault. A patient with primary involvement of the calvaria in the setting of SAPHO syndrome is described here, which, to the authors' knowledge, is the first report of such localization. The clinically and radiologically benign evolution of the different stages of the bone lesions is presented. The authors suggest that the SAPHO syndrome should be considered in the differential diagnosis of lytic, sclerotic, or hyperostotic lesions of the skull, particularly before considering invasive diagnostic procedures.

Acquired Hyperostosis Syndrome↗

PubMed1999

HIV-associated primary CNS lymorbidity and utility of brain biopsy.

INTRODUCTION: Human immunodeficiency virus (HIV) infection is associated with several central nervous system (CNS) infections and neoplasms. These opportunistic processes generally occur with advanced immunosuppression, but if an accurate diagnosis is made, effective treatment can frequently be initiated. METHODS: In an attempt to assess the safety, diagnostic yield, and utility of stereotactic brain biopsy in the clinical management of suspected HIV-associated primary CNS lymphoma, we retrospectively studied the performance of biopsy in HIV-seropositive patients presenting with focal intracranial lesions. This analysis included 435 patients undergoing brain biopsy, identified through a local case series (n=47) combined with all published cases (n=388). The years of analysis for this study were 1984 and 1997. We also assessed the survival of HIV-associated intracranial mass lesions and of PCNSL patients treated at JHU. RESULTS: Definitive histopathological diagnoses were established in eighty-eight percent of biopsied cases: primary CNS lymphoma (PCNSL) (30%), CNS toxoplasmosis (CNS TOXO) (16%), progressive multifocal leukoencephalopathy (PML) (25%), and other specific diagnoses (17%). Post-biopsy morbidity within thirty days was 8.4% and mortality was 2.9%. PCNSL was the most common diagnosis among cases biopsied after failure of anti-toxoplasmosis therapy, 134/205 (65%). In the local case series, biopsy-related morbidity was associated with poor functional status, decreased platelet count, and number of lesions at presentation. The median survival of irradiated PCNSL cases was 29 days longer than untreated cases (median survival 50 days versus 21 days, respectively, Chi-square=6.73, P<0.01). DISCUSSION: Stereotactic brain biopsy had a high diagnostic yield for HIV-associated focal intracranial lesions, however, the biopsy complication rate in this patient population was relatively high. PCNSL was diagnosed in the majority of patients failing anti-toxoplasmosis therapy. Survival after irradiation for PCNSL remains very poor.

AIDS Dementia Complex↗

PubMed1999

Intracranial leiomyosarcoma in a patient with AIDS.

We report an intracranial leiomyosarcoma in the pontine cistern of a 34-year-old woman infected with the human immunodeficiency virus (HIV). The clinical, radiological and pathological data are reviewed. The tumor was Epstein-Barr virus (EBV) positive by in situ hybridization. This case emphasizes that smooth muscle neoplasms arising in the setting of immunocompromise can occur intracranially, and corroborates a hypothesis that EBV coinfection may have a role in development of these tumors.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Ictus expectoratus: a sign of complex partial seizures usually of non-dominant temporal lobe origin.

Spitting (or expectoration) is rarely seen with seizures. In Western society, spitting is a striking behavioral aberration. A 13-year-old child had intermittent agitated behavior, episodes of rage, spitting and confusion lasting up to 2 minutes. He stood up in church and told the preacher to 'shut up and sit down'. Epilepsy monitoring revealed spitting with polysharp and spike seizures resolved over the right temporal lobe. Magnetic resonance imaging revealed a right temporal lobe ganglioglioma. Spitting seizures resolved after resection. Ictal expectoration is rare. It may occur with epigastric aura, nausea, chewing, swallowing and fumbling. Literature review disclosed 17 cases, 12 of which arose from the non-dominant hemisphere. Most regressed with surgery and anticonvulsants.

Adolescent↗

PubMed1998

Transitional cell carcinoma presenting as a solitary brain lesion: a case report and review of the world literature.

Transitional cell carcinoma of the urinary tract will account for roughly 50,000 new cases of cancer in the US this year. Metastatic involvement to the brain is uncommon with this malignancy. When it does occur, it is usually in the setting of widespread metastatic disease. A rare case of transitional cell carcinoma of the bladder presenting as a solitary brain lesion is reported. In addition, we reviewed the world literature regarding transitional cell carcinoma metastatic to the central nervous system. Our review suggests that metastatic transitional cell carcinoma of the central nervous system has become increasingly common as more effective chemotherapeutic regimens have been developed to control the primary disease. The recent literature also suggests that, much like other metastatic disease to the brain, outcome and survival in patients without widespread disease is improved by aggressive surgical and oncological management.

Aged↗

PubMed1998

Well-differentiated papillary adenocarcinoma arising in a supratentorial enterogenous cyst: case report.

OBJECTIVE AND IMPORTANCE: We report a case of a well-differentiated papillary adenocarcinoma arising in an supratentorial enterogenous cyst. The clinicopathological features of this case and a brief review of the literature are presented. CLINICAL PRESENTATION: A 45-year-old woman presented with abrupt onset of sensory seizures and abnormal sensation on the left side of her face, left leg, and left arm. Radiological studies showed a cystic extraaxial tumor with mass effect in the right parietal area. The initial clinical impression was a metastatic lesion, and a comprehensive metastatic workup revealed no evidence of tumor elsewhere. INTERVENTION: A gross total resection of the solid cystic tumor was achieved by a frontoparietal craniotomy. Sixteen months after the initial surgery, the patient presented with signs of increased intracranial pressure and a large parietal cyst. The cyst was fenestrated at the time of the second craniotomy. CONCLUSION: A pathological study of the initial surgical material revealed it to be a well-differentiated papillary adenocarcinoma in association with an enterogenous cyst. The second surgical specimen consisted only of the benign cyst wall. The patient recovered uneventfully from the second surgery and was free of symptoms 6 months postoperatively. The importance of recognizing the rare possibility of malignant progression of a benign enterogenous cyst in the central nervous system is discussed.

Adenocarcinoma, Papillary↗

PubMed1997

Neoplastic meningitis following surgical resection of isolated cerebellar metastasis: a potentially preventable complication.

Neoplastic meningitis (NM) occurs in approximately 8% of all cancer patients. To confirm a clinical impression that NM is relatively common in patients who undergo surgical resection of an isolated cerebellar metastasis (ICM), a retrospective study was performed. All patients who underwent a surgical resection of an isolated CNS metastasis at The Johns Hopkins Hospital between January 1991 and June 1993 were identified. Their charts, laboratory and pathologic data, radiologic studies, survival and cause of death were reviewed. A total of 66 patients were identified fifty-five patients underwent a surgical resection of a supratentorial metastasis while 11 patients (6 females and 5 males) underwent a surgical resection of an isolated cerebellar metastasis. The ages of patients with cerebellar metastases ranged from 23 to 74 years at the time of diagnosis with a median age of 49 years. All 11 patients had stable systemic disease and an excellent performance status. Five patients had tumors from lung, 2 from breast, and 4 from other sites. Each was expected to have a long survival. However, 4 of the 11 patients (36%) developed unequivocal NM at 1, 3, 6, and 7 months following surgical resection and all died within 1 month from the diagnosis of NM. Two patients had a positive CSF cytology and the other two had multiple enhancing leptomeningeal metastases on MRI. Two additional patients died of progressive neurological disease without evidence of local recurrence, yet were never formally evaluated for NM and two were lost to follow-up. Thus, the incidence of NM in this patient population is at least 36%. In the 55 patients who had resections of supratentorial metastases, only 1 patient (2%) developed NM. This study suggests that NM following surgical resection of an ICM may be common and may result in the premature demise of patients with excellent performance status, minimal systemic disease, and a reasonable life expectancy. Further studies are needed to determine if prophylactic intrathecal chemotherapy administered perioperatively could diminish the incidence of clinically apparent NM in this patient population.

Adult↗

PubMed1996

Interstitial delivery of carboplatin via biodegradable polymers is effective against experimental glioma in the rat.

PURPOSE: Carboplatin has shown promise experimentally as an antineoplastic agent against both primary central nervous system (CNS) tumors and several solid tumors that frequently metastasize to the brain. Unfortunately, carboplatin is limited in its clinical use for tumors in the CNS by systemic toxicity and poor penetration through the blood brain barrier. Recent advances in polymer technology have made feasible the intracranial implantation of a biodegradable polymer capable of local sustained delivery of chemotherapy for brain neoplasms. This study assessed the toxicity and efficacy of carboplatin delivered from intracranial sustained release polymers in the treatment of experimental gliomas in rodents. METHODS: Two biodegradable anhydride polymer systems were tested: a copolymer of 1,3-bis-(p-carboxyphenoxy propane) and sebacic acid, and a copolymer of fatty acid dimer and sebacic acid. The polymers were loaded with carboplatin and dose escalation studies evaluating toxicity were performed by implanting carboplatin-loaded polymers into the brains of rats. Next, efficacy was tested. F-98 glioma cells were injected intracranially into rats, and 5 days later polymers containing the highest tolerated doses were implanted at the site of tumor growth. The survival of animals receiving carboplatin-loaded polymer was compared with that of animals receiving intraperitoneal doses of the same agent. RESULTS: Carboplatin-polymer was well tolerated at doses up to 5% loading in both polymer systems. Locally delivered carboplatin effectively prolonged survival of rats with F98 gliomas. Maximal treatment effect was seen with 5% loading of either polymer, with median survival increased threefold over control (P < 0.004). Systemic carboplatin also significantly prolonged survival, but the best intracranial polymer dose was significantly more effective than the best systemic dose tested. CONCLUSIONS: Carboplatin can be safely delivered intracranially by biodegradable sustained- release polymers. This treatment improves survival in rodents with experimental gliomas, with locally delivered carboplatin being more effective than systemic carboplatin.

Animals↗

PubMed1995

Neurite outgrowth in PC12 cells stimulated by acetyl-L-carnitine arginine amide.

Senescence of the central nervous system is characterized by a progressive loss of neurons that can result in physiological and behavioral impairments. Reduction in the levels of central neurotrophic factors or of neurotrophin receptors may be one of the causes of the onset of these degenerative events. Thus, a proper therapeutic approach would be to increase support to degenerating neurons with trophic factors or to stimulate endogenous neurotrophic activity. Here we report that acetyl-L-carnitine arginine amide (ST-857) is able to stimulate neurite outgrowth in rat pheochromocytoma PC12 cells in a manner similar to that elicited by nerve growth factor (NGF). Neurite induction by ST-857 requires de novo mRNA synthesis and is independent of the action of several common trophic factors. The integrity of the molecular structure of ST-857 is essential for its activity, as the single moieties of the molecule have no effect on PC12 cells, whether they are tested separately or together. Also, minor chemical modifications of ST-857, such as the presence of the arginine moiety at a position other than the amino one, completely abolish its neuritogenic effect. Lastly, the presence of ST-857 in the culture medium competes with the high affinity NGF binding in a dose dependent fashion. These results, although preliminary, are suggestive of a possible role for ST-857 in the development of therapeutic strategies to counteract degenerative diseases of the CNS.

Acetylcarnitine↗

PubMed1995

Intraventricular rupture of a purulent brain abscess: case report.

The mortality of patients with brain abscesses has decreased significantly from 38% in the 1950s to 25% in the 1980s (P = 0.003, Fisher's exact test by decade of report; asymptotic P values based on chi 2 distribution with 3 degrees of freedom, 28 series, 2825 total patients). This decrease in mortality has been attributed to improved diagnostic imaging, the evolution of neurosurgical techniques and understanding of intracranial pressure pathophysiology, greater critical care understanding, and newer antibiotics. However, the mortality associated with the intraventricular rupture of brain abscesses (IVROBA) remained consistently high (at or above 80% once IVROBA was identified) throughout these decades. Although 129 cases (84.5% mortality, 20 survivors) of IVROBA were located in these series and an additional six case reports of survival after IVROBA were found in the literature, treatment advice and detailed clinical description of these surviving cases are sparse or absent. A case of IVROBA with good quality of survival is presented along with the aggressive five-component therapeutic plan used. The five components are: 1) open craniotomy with debridement of abscess cavity, 2) lavage of the ventricular system, 3) 6 weeks of intravenous antibiotics, 4) intraventricular gentamicin twice daily for 6 weeks, and 5) intraventricular drainage for 6 weeks.

Brain Abscess↗

PubMed1995

Effectiveness of controlled release of a cyclophosphamide derivative with polymers against rat gliomas.

Most malignant gliomas grow despite treatment by standard chemotherapeutic agents. The authors explored the use of an innovative drug, 4-hydroperoxycyclophosphamide (4HC), delivered via a controlled-release biodegradable polymer to determine whether local delivery would enhance efficacy. This drug is an alkylator-type chemotherapeutic agent derived from cyclophosphamide. Unlike the parent drug, which requires activation by hepatic microsomes, 4HC is active in vitro. Two rat glioma cell lines, 9L and F98, were treated in cell culture with medium containing 4HC. Both cell lines were more sensitive to 4HC than to a nitrosourea, BCNU, an agent of established value in the local therapy of gliomas. Ninety Fischer 344 rats implanted with 9L or F98 gliomas were treated with an intracranial polymer implant containing 0% to 50% loaded 4HC in the polymer, and it was found that 20% 4HC-loaded polymers caused minimum local brain toxicity and maximum survival. These polymers were then used to compare the in vivo efficacy of 4HC to BCNU in rats implanted with 9L glioma. Animals with brain tumors treated with 4HC had a median survival span of 77 days compared to the median survival of 21 days in BCNU-treated animals and median survival of 14 days in untreated animals. Long-term survival for more than 80 days was 40% in the 4HC-treated rats versus 30% in the BCNU-treated rats. The polymer carrier used in this study was a copolyanhydride of dimer erucic acid and sebacic acid 1:1, which was able to maintain the hydrolytically unstable 4HC in a stable state for local delivery. Thus, it is concluded that 4HC-impregnated polymers provide an effective and safe local treatment for rat glioma.

Animals↗

PubMed1995

Intratumoral chemotherapy.

In an effort to improve survival from malignant gliomas, investigators have used intratumoral chemotherapy protocols to deliver high doses of tumoricidal agents directly to the brain. Theoretically, these infusions bypass the blood-brain barrier, minimize systemic drug levels and the side effects of chemotherapy, and achieve prolonged elevations of intracerebral chemotherapeutic agents relative to those obtainable by systemic administration. Almost all major classes of chemotherapeutic agents have been examined as possible intratumoral therapies via delivery approaches ranging from simple intratumoral injections to implantable computer-driven constant infusion pumps and biodegradable polymer matrices. In this review, we summarize the major clinical trials and experimental investigations underlying the development of intratumoral chemotherapy as a treatment for gliomas.

Animals↗