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D Barba

Publications and source records attributed to D Barba.

At least 19 recordsLinked to original sources

Case of the month: March 1999--A 26 year old HIV positive male with dura based masses.

A 26-year-old male with AIDS presented with a chief complaint of headaches and neck pain. An MRI revealed two enhancing extra-axial dura based masses, one in the area of the left sphenoid wing and one at the level of C2-3. In both cases, microscopic sections showed actin positive spindle cell neoplasms with long slender nuclei, consistent with leiomyomas. Both tumors were positive for Epstein Barr virus by in situ hybridization. This case report serves to emphasize the importance of considering soft tissue tumors such as leiomyoma in the differential diagnosis of mass lesions that occur in the central nervous system in AIDS and discusses the role of EBV in tumorigenesis.

Acquired Immunodeficiency Syndrome↗

Complications associated with intraventricular chemotherapy in patients with leptomeningeal metastases.

The authors studied complications associated with intraventricular chemotherapy in patients with leptomeningeal metastases (LM). One hundred twenty consecutive patients with LM (71 females and 49 males) ranging in age from 10 to 72 years (median 42 years) were treated with involved-field radiotherapy and intraventricular chemotherapy using an Ommaya reservoir and intraventricular catheter system. The diagnosis of LM was determined by a combination of clinical presentation (114 patients); cerebrospinal fluid cytological studies (100); or neuroradiographic studies (42). Systemic tumor histological findings included breast (34 patients); non-Hodgkin's lymphoma (22); melanoma (16); primitive neuroectodermal tumors including medulloblastoma (10); glial neoplasms, leukemia, small cell lung, nonsmall cell lung, and colon (six each); prostate and kidney (three each); and gastric cancers (two). Sixteen patients, all with non-Hodgkin's lymphoma, also had acquired immune deficiency syndrome. Patients received one to four (median two) chemotherapeutic drugs and underwent a total of 1110 cycles of intraventricular chemotherapy (median 10). Intraventricular chemotherapy administration and diagnostic Ommaya reservoir punctures totaled 4400, with a median of 46 per patient. Complications included aseptic/chemical meningitis (52 patients); myelosuppression due to intraventricular chemotherapy (21); catheter-related infections (nine); unidirectional catheter obstruction (six); intraventricular catheter malpositioning (two); Ommaya reservoir exposure (two); leukoencephalopathy (two); and chemotherapy-related myelopathy (one). There were no treatment-related deaths; however, seven patients (6%) required additional surgery for either catheter repositioning (two) or reservoir removal (five). Seven patients with catheter-related infections were treated successfully with intraventricular and systemic antibiotic drugs, thereby preserving the Ommaya system. The authors conclude that Ommaya reservoirs are convenient and pharmacologically rational systems for administering intraventricular chemotherapy. Overall, serious complications requiring surgery are infrequent (6%) and most often secondary to catheter infections, Ommaya reservoir exposure, or initial catheter malpositioning. In the majority of instances, catheter infections may be managed medically, as may the most common complications of intraventricular chemotherapy including aseptic meningitis (43% of patients) and myelosuppression (18%).

Adolescent↗

Concurrent cisplatin therapy and iodine 125 brachytherapy for recurrent malignant brain tumors.

OBJECTIVE: Toxicity and safety study of concurrent cisplatin therapy and iodine 125 (125I) brachytherapy. BACKGROUND: Iodine 125 brachytherapy has an established role in surgically accessible recurrent tumors of brain. Cisplatin has antitumoral activity against glial neoplasms and has demonstrated sensitization of tumor to radiotherapy. DESIGN/METHODS: In 16 patients (age range, 13 to 68 years, median, 47 years), stereotactically placed catheters were afterloaded with 125I sources. A median 50-Gy minimum treatment volume dose was delivered during a 100-hour period along with cisplatin (20 mg/m2 per day for 5 days). Histologic diagnoses included glioblastoma multiforme (n = 11), anaplastic astrocytoma (n = 3), ependymoma (n = 1), and anaplastic oligodendroglioma (n = 1). Tumor volumes ranged from 7.0 to 73 cm3 (median, 25 cm3). RESULTS: Early complications included headache (n = 7), transient exacerbations of preexisting neurologic deficits (n = 5), seizures (n = 3), and nausea/vomiting (n = 3). Late complications included steroid dependency (n = 10), progressive dementia in the absence of recurrent tumor (n = 1), and radiation-induced necrosis (n = 9) requiring reoperation (n = 9). Fifteen of 16 patients were assessable, with a median follow-up time of 9.5 months. Brachytherapy was discontinued in one patient owing to an acute subdural hematoma. A partial response was seen in five patients, disease remained stable in seven patients, and disease progressed in three patients. CONCLUSIONS: We conclude that 125I brachytherapy with concurrent cisplatin therapy is associated with an acceptable level of toxic effects and warrants further investigation.

Adolescent↗

Early biopsy versus empiric treatment with delayed biopsy of non-responders in suspected HIV-associated cerebral toxoplasmosis: a decision analysis.

OBJECTIVE: To construct and evaluate a decision analytic model of proposed management strategies for HIV-infected patients presenting with cerebral mass lesions, radiographically compatible with toxoplasmosis, lymphoma, or other etiologies, assuming knowledge of Toxoplasma antibody status in serum. METHODS: Using decision analysis, we evaluated two management strategies, for patients found to be either Toxoplasma-seropositive or -negative, for whom an initial choice was made for early brain biopsy (EB) or for empiric therapy with delayed biopsy (ETDB) of non-responders. The outcome to be optimized was the percentage of patients alive at 12 months. Model variables included predictive value of toxoplasmosis serology, probabilities of treatment response and death within 14-21 days conditional on correct diagnosis, probability of operative death, probabilities of non-diagnostic brain biopsy conditional both on correct diagnosis and prior treatment. RESULTS: One and two-way sensitivity analyses, by Toxoplasma serostatus, led to the following conclusions (1) for Toxoplasma-seropositive patients, ETDB gives nearly equivalent outcomes to EB of all patients; (2) for Toxoplasma-seronegative patients, although both strategies have equivalent outcomes under baseline assumptions, EB is preferred if there are even small survival advantages for early versus delayed diagnosis of lymphoma or other conditions, or if risk of death within 14-21 days of ET exceeds 10% when correct diagnosis is not toxoplasmosis. CONCLUSION: Under plausible assumptions, Toxoplasma-seronegative patients will benefit from an early biopsy strategy.

Biopsy↗

Stereotactic radiosurgery for recurrent gliomas.

BACKGROUND: The treatment of recurrent gliomas is palliative; however, the local pattern of tumor recurrence permits retreatment with single fraction, high dose stereotactic radiotherapy or radiosurgery (RS). METHODS: Twenty patients (median Karnofsky performance status, 80), aged 8-62 years with recurrent gliomas, were treated with RS after failing adjuvant therapy. Tumor histologies included glioblastoma multiforme (5), anaplastic astrocytoma (10), fibrillary astrocytoma (4), and primitive neuroectodermal tumor (1). Tumor volumes ranged from 3-53.5 cc, with a median of 17 cc. RESULTS: Seven early and one late radiation complication were seen. All seven early radiation complications were due to raised intracranial pressure and resolved in all but one patient who died. Median follow-up in 19 evaluable patients was 8 months (range, 2-29 months). Fourteen patients died from progressive tumor (median survival, 7 months). Five patients, four with recurrent tumor, were alive (median follow-up, 19 months) with a median time-to-tumor progression of 9 months. CONCLUSIONS: Radiosurgery demonstrates modest efficacy with acceptable toxicity in selected patients with recurrent gliomas and warrants further investigation.

Adolescent↗

Development of anti-tumor immunity following thymidine kinase-mediated killing of experimental brain tumors.

Using the 9L experimental brain tumor model, we studied long-term tumor regression and immunologic consequences of tumor killing in a model of in vivo gene transfer of the herpes simplex virus 1 thymidine kinase (HSV-TK) gene and ganciclovir (GCV) treatments. Fibroblasts modified to produce retroviral vectors carrying the HSV-TK gene were implanted into established 9L brain tumors in Fischer 344 rats to carry out gene transfer. Animals were then treated with parenteral GCV. Significant tumor regression was seen following GCV treatments in short-term experiments (17 days) as quantified by measurements of tumor volume. In long-term studies, 7 of 32 (22%) treated animals survived 90 days. Histologic examination of the brains of the successfully treated animals demonstrated residual tumor cells and inflammatory cells consisting predominantly of macrophages/microglia and T cells in the hemisphere with the residual tumor cyst. Rats surviving 90 days rejected repeat tumor injections into the contralateral brain and flank, whereas identical tumor injections in naive animals resulted in both brain and flank tumors. The presence of significant anti-tumor immunity following HSV-TK and GCV treatments suggests that the immune system plays a critical role in the sustained tumor regressions associated with these treatments. These findings show that while HSV-TK and GCV treatments can result in long-term tumor regressions in this model, the success of these treatments could be improved by better understanding the role played by the host's immune systems.

Animals↗

Multiple plasma cell granulomas of the central nervous system: case report.

Plasma cell granulomas of the central nervous system are exceedingly rare. Of the six well-documented cases that have been published to date, five plasma cell granulomas were intracranial and one was located in the spinal meninges. Multiple plasma cell granulomas of the central nervous system have not previously been reported. We now report a patient who had two plasma cell granulomas in the spinal meninges and one in the anterior cerebral falx. The histological findings that differentiate this rare lesion from other central nervous system lesions, such as plasmacytoma and meningioma, are discussed with a review of the literature.

Brain Diseases↗

Evaluation and implementation of a needleless intravenous system: making needlesticks a needless problem.

A needleless intravenous (IV) system with blunt plastic cannulas and specially designed injection sites was introduced at Olive View Medical Center to reduce needlestick injuries, particularly IV-related needlesticks. IV-related needlestick injuries decreased 72% during the first 8 months of use, costs were reduced $1.85 for a typical IV piggyback administration set-up by revising the IV piggyback procedure, and a staff survey revealed satisfaction with the new system.

California↗

Thymidine kinase-mediated killing of rat brain tumors.

Gene therapy has many potential applications in central nervous system (CNS) disorders, including the selective killing of tumor cells in the brain. A rat brain tumor model was used to test the herpes simplex virus (HSV)-thymidine kinase (TK) gene for its ability to selectively kill C6 and 9L tumor cells in the brain following systemic administration of the nucleoside analog ganciclovir. The HSV-TK gene was introduced in vitro into tumor cells (C6-TK and 9L-TK), then these modified tumor cells were evaluated for their sensitivity to cell killing by ganciclovir. In a dose-response assay, both C6-TK and 9L-TK cells were 100 times more sensitive to killing by ganciclovir (median lethal dose: C6-TK, 0.1 microgram ganciclovir/ml; C6, 5.0 micrograms ganciclovir/ml) than unmodified wild-type tumor cells or cultured fibroblasts. In vivo studies confirmed the ability of intraperitoneal ganciclovir administration to kill established brain tumors in rats as quantified by both stereological assessment of brain tumor volumes and studies of animal survival over 90 days. Rats with brain tumors established by intracerebral injection of wild-type or HSV-TK modified tumor cells or by a combination of wild-type and HSV-TK-modified cells were studied with and without ganciclovir treatments. Stereological methods determined that ganciclovir treatment eliminated tumors composed of HSV-TK-modified cells while control tumors grew as expected (p < 0.001). In survival studies, all 10 rats with 9L-TK tumors treated with ganciclovir survived 90 days while all untreated rats died within 25 days. Curiously, tumors composed of combinations of 9L and 9L-TK cells could be eliminated by ganciclovir treatments even when only one-half of the tumor cells carried the HSV-TK gene. While not completely understood, this additional tumor cell killing appears to be both tumor selective and local in nature. It is concluded that HSV-TK gene therapy with ganciclovir treatment does selectively kill tumor cells in the brain and has many potential applications in CNS disorders, including the treatment of cancer.

Animals↗

Specific genetic change in tumors associated with von Hippel-Lindau disease.

Previous reports showed that the loss of DNA sequences on the short arm of chromosome 3 (3p) is consistently found in sporadic renal cell carcinomas. To evaluate the significance of this genetic change, we looked for the loss of 3p alleles in hereditary renal cell carcinomas and other tumors from patients with von Hippel-Lindau disease. Specific loss of alleles from chromosome 3p was detected with polymorphic DNA markers in 11 renal cell carcinomas, one pheochromocytoma, two spinal hemangioblastomas and one cerebellar hemangioblastoma from von Hippel-Lindau patients. Multiple renal cell carcinomas in individuals with von Hippel-Lindau disease showed loss of the same chromosome 3p alleles, which demonstrated that the same chromosome was deleted in each tumor. Analysis of haplotypes indicated that the loss of chromosome 3p alleles was from the chromosome bearing the balancing, wild-type allele of the VHL gene. These results are consistent with the concept that the VHL gene is a recessive oncogene. Renal cell carcinoma, pheochromocytoma, and spinal and cerebellar hemangioblastomas develop in predisposed family members when somatic mutational events lead to loss of chromosome 3p sequences bearing the wild-type allele of the VHL gene.

Alleles↗

Intratumoral LAK cell and interleukin-2 therapy of human gliomas.

Adoptive immunotherapy using lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2) offers the possibility of a new treatment for patients with malignant glial tumors. In a clinical trial, the effectiveness of a 5-day treatment cycle of direct intratumoral administration of both LAK cells and IL-2 via a reservoir/catheter system in patients with recurrent malignant gliomas was studied. Ten patients were entered into the study, nine of whom were treated with 15 cycles of LAK cells (0.9 to 21.0 x 10(9) cells) and IL-2 (49 to 450 x 10(3) U/kg). The 10th patient in the study was not treated because of the onset of severe neurological deficits prior to beginning immunotherapy. Of the nine patients treated, one had a partial tumor response to immunotherapy as documented by computerized tomography. Neurological side effects occurred in all patients undergoing treatment and were related to increases in cerebral edema that appeared to be mediated by the immunotherapy. This report demonstrates the present limitations of regional adoptive immunotherapy with LAK cells and IL-2 in the treatment of human glial tumors.

Adolescent↗

The effect of intravenous interleukin-2 on brain water content.

Parenteral treatment with interleukin-2 (IL-2) is effective against certain advanced cancers outside the central nervous system. Prior to commencement of Phase II trials in patients with brain tumors, the neurological and neuroradiological features of 10 patients treated with intravenous administration of repeated doses of IL-2 were studied. Three patients had malignant gliomas, and seven patients had extracranial cancer without evidence of intracranial metastasis. All were treated with intravenous doses of 10(5) U/kg three times daily for up to 5 days. The patients with gliomas received cranial computerized axial tomography (CT) scans before IL-2 therapy was initiated and during the later stages of treatment. The patients with extracranial cancer underwent T2-weighted magnetic resonance (MR) imaging before and later during therapy. After two to 11 doses of IL-2, the patients with gliomas had marked neurological deterioration that was associated with a mild to marked increase in peritumoral edema and mass effect visible on CT scans. With cessation of treatment and appropriate supportive care, all returned to their pretreatment state. The patients with extracranial cancer were either neurologically unchanged or underwent minor transient changes in mental status (lethargy and confusion). In these patients, the MR signal intensity was quantified and compared in eight anatomic regions of interest. In six of the seven patients, there were increases in gray and white matter signal intensity consistent with increased cerebral water content. The percentage changes (means +/- standard error of the means) were 12.6% +/- 7.3% in the gray matter and 17.0% +/- 6.2% in the white matter. This study demonstrates that treatment with a high parenteral dose of IL-2 is not tolerated by patients with gliomas due to increased cerebral edema. In patients with extracranial cancer but no brain disease, parenteral IL-2 induces an increase in the cerebral water content of both gray and white matter.

Brain Chemistry↗

Pharmacokinetics of ciprofloxacin in impaired liver function.

The pharmacokinetics of ciprofloxacin after a single 500 mg oral dose was studied in one group of healthy volunteers and in patients affected by liver cirrhosis and classified into three groups according to Child-Turcotte criteria. The serum concentrations were determined by an agar well diffusion assay 0.5, 1, 3, 6, 12 and 24 h after the administration of the drug. No significant differences were noticed in Cmax, Tmax, T1/2 and AUCtot in the group A and B of patients and in the control group. Class C patients showed on the other hand a Cmax 15-25% higher than in other groups (2.74 mcg/ml), a T1/2 1.12-1.42 hours longer than in other groups and a consequent much higher AUCtot (17.70 mcg/h/ml). The concomitant administration of diuretics of anti-H2 drugs was also evaluated as possible factors affecting the ciprofloxacin pharmacokinetics, but no significant differences were noticed. A mild or moderate impairment of the liver function did not affect the pharmacokinetics of ciprofloxacin, but the severe impairment of the liver function could affect its Cmax and serum half-life, so that further studies with multiple doses will be needed to evaluate if any dosage adjustment would be required in these patients.

Adult↗

Morphology of interleukin-2-stimulated human peripheral blood mononuclear effector cells killing glioma-derived tumor cells in vitro.

This is the first morphological study of interleukin-2-stimulated human peripheral blood mononuclear (PBM) cells resulting in lymphokine-activated killer (LAK) cell activity against human glioma-derived tumor cells in vitro, in which high-resolution differential interference video light microscopy, scanning electron microscopy, and transmission electron microscopy were used. A subset of cells within the LAK cell population are the effector cells and have an asymmetric cellular architecture characteristic of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Upon binding to target cells, the LAK effector cell nucleus is positioned away from the target cell, whereas the granules, Golgi apparatus, and microtubules orient toward the target cell. These LAK-glioma cell conjugates form very tight plasma membrane bonds with numerous interdigitations, and vesicles were found in the small extracellular spaces between the cells. This morphology was not observed in unstimulated PBM-glioma cell co-cultures. Glioma-derived cells react to LAK effector cells by blebbing, becoming round, and rapidly detaching from the substrate. The injured glioma-derived cells had a highly condensed cytoplasm and chromatin, lobular nucleus, and severe plasma membrane blebs, which are consistent with an apoptotic rather than an osmotic lysis mechanism of cell death. This study provides morphological evidence that supports a common cytotoxic mechanism for CTLs, NK cells, and LAK effector cells. The cytotoxic mechanism is based on the local exocytosis of vesicles by the effector cell into the small extracellular space between the effector-target cell conjugate. Granules found in CTLs, NK cells, and LAK cells contain a pore-forming protein that inserts holes in the target cell's plasma membrane through which a lethal substance(s) not yet identified is thought to enter the cell.

Cell Line↗

Efficacy and safety of ciprofloxacin in the treatment of UTIs and RTIs in patients affected by liver diseases.

The clinical efficacy and the safety of ciprofloxacin was studied in 92 patients (aged 26 to 83 years; mean 57.5 years) affected by urinary tract infections (UTI) and respiratory tract infections (RTI) suffering also with various liver diseases. Ciprofloxacin was given orally at different dose regimens: 500 mg b.i.d. (22 cases), 250 mg b.i.d. (20 cases), 500 mg s.i.d. (20 cases) for the treatment of UTIs; 500 mg b.i.d. (ten cases) and 250 mg b.i.d. (20 cases) for the treatment of RTIs. The doses were not correlated to the severity of the infections. Patients were treated for five to 15 days. All the bacteria isolated from sputum or urine before treatment were sensitive to ciprofloxacin (MIC range less than or equal to 0.015 mg/l to 8 mg/l). The clinical and bacteriological responses were favourable in a high percentage of patients both for RTIs and UTIs, irrespective of the dose. Side effects were infrequent (7%) and mild (nausea, gastralgia, oral candidosis), never requiring the interruption of the treatment. No change in the blood chemistry tests was observed at any dose.

Adult↗

Penetration of recombinant interleukin-2 across the blood-cerebrospinal fluid barrier.

Recombinant interleukin-2 (rIL-2) is an immunotherapeutic agent with efficacy against certain advanced cancers. The penetration of rIL-2 across the blood-cerebrospinal fluid (CSF) barrier was studied in 12 cancer patients who had no evidence of tumor involvement of the central nervous system. At different times during treatment with intravenous rIL-2, CSF was withdrawn either continuously for 8 to 26 hours via a lumbar subarachnoid catheter (in eight patients) or by a single lumbar puncture (in four). Bioassay showed the appearance of rIL-2 in lumbar CSF 4 to 6 hours after the first intravenous dose, a rise over 2 to 4 hours to a plateau of 3 to 9 U/ml, and clearance to less than 0.1 U/ml by 10 hours after the last dose. An abnormally elevated CSF albumin level in two of the twelve patients indicated alteration of the blood-brain barrier. There were no abnormalities in the CSF glucose level or white blood cell count. The CSF pharmacokinetics contrast with the rapid elimination of rIL-2 from plasma and demonstrate significant blood-CSF barrier penetration. These data support the possibility of achieving CSF levels of rIL-2 that are adequate to maintain activity of lymphokine-activated killer cells after parenteral administration, and argue for rIL-2-associated disruption of the human blood-brain barrier in some patients.

Antineoplastic Agents↗

Clinical efficacy and safety of sulbactam/ampicillin in patients suffering from chronic liver disease.

Sulbactam is a new beta-lactamase inhibitor with pharmacokinetic characteristics in humans similar to those of ampicillin. A total of 41 patients hospitalized in the Clinic of Infectious Diseases, University of Naples, for chronic liver diseases, were treated with sulbactam/ampicillin (ratio 1:2) for urinary, respiratory, biliary tract or soft tissue infections. Sulbactam/ampicillin was administered im or iv at a dosage of 3-9 g/day depending on the site and severity of the infection. All the patients treated with sulbactam/ampicillin had clinical signs and symptoms of infection, and all the organisms isolated were sensitive to sulbactam/ampicillin (MIC less than 16 mg/l). For both Gram-positive and Gram-negative bacteria the sulbactam/ampicillin MICs were much lower than the ampicillin MICs. In agreement with the favourable in-vitro results, we observed good therapeutic efficacy. 85% of the patients recovered or improved within a few days of therapy, with no clinical relapses, and in 81% of the infections the responsible bacteria were completely eradicated. We observed a low number of side effects (3/41 oral candidosis; 3/41 pain at the im injection site) and no change in the blood chemistry tests.

Adult↗