Treatment of refractory recurrent malignant glioma with adoptive cellular immunotherapy: a case report.

We report the successful treatment of a patient with recurrent malignant glioma with adoptive cellular immunotherapy. The patient is a young adult with recurrent progressive disease refractory to aggressive multi-modality therapy including repetitive surgical resection, radiation, radiosurgery and chemotherapy. He received multiple courses of local administration of autologous lymphokine-activated killer (LAK) cells in combination with a low dose of interleukin-2 (IL-2) through an Ommaya reservoir-catheter system. The side-effects of this treatment were limited and manageable. The patient achieved a complete remission, as demonstrated by MRI and confirmed by glucose-positron emission tomography (PET) imaging 11 months after initiation of immune therapy. Twenty-six months later, the patient is still in remission with improving performance status. Adoptive cellular immunotherapy utilizing autologous LAK cells with low dose IL-2 appears to be a safe and effective therapy for a subset of patients with primary, recurrent or progressive malignant glioma following conventional therapy.

Treatment of recurrent glioblastoma multiforme using fractionated stereotactic radiosurgery and concurrent paclitaxel.

Despite the progress in neurosurgery and radiotherapy, almost all patients treated with malignant gliomas develop recurrent tumors and die of their disease. Eighty-eight patients (median age 56 years) with recurrent glioblastoma (median tumor volume 32.7 cm3) were treated with noninvasive fractionated stereotactic radiosurgery and concurrent paclitaxel used as a sensitizer. The median interval between diagnosis of primary glioblastoma and salvage radiosurgery was 7.8 months. Four weekly treatments (median dose: 6.0 Gy) were delivered after the 3-hour paclitaxel infusion (median dose: 120 mg/m2). Survival was calculated by the Kaplan-Meier method from radiosurgery treatment. Overall median survival was 7.0 months, and the 1-year and 2-year actuarial survival rates were 17% and 3.4%, respectively. When grouped by performance status, there was no difference in survival between the patients with low and high Karnofsky score. Patients with tumor volume less than 30 cm3 survived significantly longer than those with tumor greater than 30 cm3 (9.4 vs. 5.7 months, p = 0.0001). Their 1-year survival rate was 40% and 8%, respectively. Eleven patients (11%) had reoperation because of expanding mass. Stable disease was seen in 40% of patients (n = 34), and increase in radiographically detected mass was observed in 41 patients (48.8%). Although the treatment of recurrent GBM is mostly palliative, the fractionated radiosurgery offers a chance for prolonged survival, especially in patients with a smaller tumor volume.

Effect of subcutaneous granulocyte colony-stimulating factor injectate volume on drug efficacy, site complications, and client comfort.

PURPOSE/OBJECTIVES: To determine the effect of administering 1.6 ml (480 mcg) of granulocyte colony-stimulating factor (G-CSF) in one subcutaneous injection or two injections of 0.8 ml each. DESIGN: Experimental. SETTING: 27-bed bone marrow transplant intensive care unit of a metropolitan, university medical center in the southwestern United States. SAMPLE: Nonprobability; 76 women who received high-dose chemotherapy for breast cancer followed by hemopoietic rescue. METHODS: Subjects were randomized into an experimental group that received one injection per 480 mcg dose and a control group that received two injections per 480 mcg dose administered by research associates using a standardized injection technique. MAIN RESEARCH VARIABLES: Injectate volume. The number of days post-transplant until the absolute neutrophil count (ANC) returned to 1,000/mm3, the incidence and surface area in mm2 of site complications, and scores on Tursky's Quantified Pain Descriptor immediately following the injection(s). FINDINGS: No significant difference existed between the two groups in ANC recovery time, frequency or size of site complications, or intensity, reaction, or sensation of discomfort reported. CONCLUSIONS: Administering 1.6 ml doses of G-CSF in one injection instead of two does not result in slower ANC recovery, induration, more frequent or larger bruises or areas of erythema, or greater client discomfort. IMPLICATIONS FOR NURSING PRACTICE: Administering one injection instead of two may decrease patients' anxiety, the nursing time needed for preparation and administration of injections, patient instruction for self-administration, the potential for contamination of vials or loss of dose, and the cost of supplies.

Recurrent glioblastoma multiforme: potential benefits using fractionated stereotactic radiotherapy and concurrent taxol.

UNLABELLED: A pilot protocol to treat recurrent glioblastoma was developed using fractionated stereotactic radiosurgery with concurrent intravenous Taxol as a radiation sensitizer. METHODS: The treatment outcome was analyzed in two groups of patients with recurrent glioblastoma. Group 1 was analyzed retrospectively, and consisted of 9 patients with a median tumor volume of 9.2 cm3 treated with single-fraction stereotactic radiosurgery alone (mean radiation dose of 19.2 Gy). In group 2, prospectively analyzed, were 14 patients treated with fractionated stereotactic radiotherapy and concurrent Taxol. RESULTS: The median survival in group 2 was 14.2 months versus 6.3 months in group 1 (p < 0.04). One-year survival for patients who received fractionated radiotherapy with Taxol was 50% compared to 11% for those treated with single-fraction radiotherapy only (p = 0.05). CONCLUSIONS: Survival for group 2 patients was significantly better compared to those treated with single-fraction radiotherapy alone. These data should stimulate the investigation of both fractionated stereotactic radiotherapy and the development of radiation sensitizers to further enhance treatment.

Acoustic neuroma: potential benefits of fractionated stereotactic radiosurgery.

BACKGROUND: Single-fraction radiosurgery of acoustic neuromas less than 3 cm in diameter is remarkable for high control but not infrequent incidence of facial and trigeminal neuropathy. Larger tumors treated surgically often result in deafness and facial neuropathy. Fractionated stereotactic radiosurgery was used in an effort to maintain effective therapy while minimizing toxicity of treatment. METHODS: The authors described 38 patients with acoustic neuromas, with age range 35-89 years (mean, 60 years). 2,000 cGy in divided weekly doses of 400 or 500 cGy was most commonly prescribed. Tumors > or = 3 cm (n = 16) received the 5 fraction schema. Mean tumor volume was 6.9 cm3, with range from 0.1 to 32.0 cm3. RESULTS: Median clinical follow-up was 27.1 months, while neuroimaging follow-up had a median of 16.3 months. All tumors were controlled. Of 23 tumors smaller than 3 cm, 14 (61%) decreased in size, and 9 showed cessation of growth. Thirteen of 16 (81%) large acoustic neuromas (3-5 cm) diminished in size. The remaining 3 showed cessation of growth. Median radiographic follow-up was 20 months, with a median clinical follow-up of 28 months. No patient developed fifth nerve symptoms after treatment nor did any patient require surgery for treatment failure. Only one had temporary seventh nerve palsy. CONCLUSION: Fractionated stereotactic radiosurgery offers a therapeutic approach producing high control rates while avoiding morbidity frequently seen after single-fraction radiosurgery or microsurgery.

Unusual lytic intraosseous meningioma.

Lytic intraosseous meningiomas are rare. This unusual case presented a diagnostic and treatment challenge.

Databases for neuroscience.

Databases for neuroscience must handle large volumes of image and graphical data as well as domain knowledge. Several software development efforts are addressing these issues in an attempt to aid the acquisition, analysis and exchange of complex data sets.

Direct effects of endotoxin on the function of the isolated perfused rat kidney.

When the endotoxin-lipopolysaccharide (LPS) derived from the cell wall of gram-negative bacteria is given to the rat in vivo, there are prompt, marked decreases in glomerular filtration rate (GFR), renal blood flow (RBF) and % Na+ reabsorption (%T-Na+). However, it has not been determined whether the endotoxin itself has a direct effect on these renal functions. To test whether endotoxin has a direct renal effect, isolated rat kidneys (N = 8) were perfused for 160 minutes with a Krebs-Ringer-HCO3- solution containing substrate-free albumin (40 g/liter), glucose (5 mM) and L(+) lactate (7.5 mM). After control observations (20 to 80 min) were made, purified LPS from E. coli was added (N = 4) to the perfusate to achieve [endotoxin] of 0.01 micrograms/ml (80 to 120 min) and 0.1 micrograms/ml (120 to 160 min). Endotoxin had no effect on GFR, Na+ reabsorption or tissue K+ content when compared to timed-control perfusions (N = 4). There was a small (approximately 10%) but significant decrease in mean perfusion flow rate (PFR) at the highest [endotoxin] when compared to the low [endotoxin]p but no change in GFR occurred. When the same LPS was given to four rats in vivo at a dose which achieved an [endotoxin] of approximately 0.08 micrograms/ml plasma, there were prompt decreases in GFR and %T-Na+ and an increase in body temperature when compared with timed-controls; there also was a large loss of K+ from the kidney tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

MR imaging of osteoid osteoma of the talus.

Magnetic resonance (MR) imaging of the painful ankle of a 15-year-old boy revealed the nidus of a subarticular osteoid osteoma of the talus along with markedly abnormal signal intensity in the neighboring bone marrow. This MR appearance correlated with alterations in the neighboring bone marrow documented by histopathologic examination.

Occipitocervical fusion. Indications, technique, and long-term results in thirteen patients.

Thirteen patients who underwent occipitocervical fusion that was performed using the same operative technique were followed for an average of 3.6 years (range, two to seven years). The indications for surgery were occipitocervical instability, neurological deficit, or intractable pain that was not responsive to non-operative treatment. Of the thirteen patients, eight had rheumatoid arthritis, two had atlanto-axial osteomyelitis, and one patient each had trauma, ankylosing spondylitis, and atlanto-occipital osteoarthritis. At follow-up, all of the thirteen patients had a solid arthrodesis and relief of severe pain in the neck. Of the ten patients who had had myelopathy preoperatively, all improved, but of four patients who had been unable to walk preoperatively because of severe motor involvement, only one was considered to be able to walk. Of the thirteen patients, ten had a satisfactory result. Occipitocervical arthrodesis using iliac grafts and the wiring technique that is described herein achieves immediate stable fixation, allowing early mobilization with a successful arthrodesis, and it should be undertaken before severe myelopathy occurs in patients who have instability of the cervical spine. The operation may optimize the patient's chances of neurological recovery.

Renal tissue citrate: independence from citrate utilization, reabsorption, and pH.

During alkalosis in vivo, renal tissue [citrate] [( citrate]t) increases and citrate reabsorption (Tcit) and utilization (Qcit) simultaneously decrease. The decrease in Qcit is interpreted to cause the increased [citrate]t, which in turn decreases Tcit X Renal citrate handling and [citrate]t could be regulated by other mechanisms, since alkalosis changes [substrate] and [H+] in extracellular (ECF) and intracellular (ICF) fluid. Also, since high plasma [citrate] decreases ionized [Ca2+] (Cai), it is not possible to determine in vivo whether there is a maximum for Tcit or Qcit and whether change in extracellular fluid (delta ECF) pH affects these maxima. We perfused the substrate-limited isolated rat kidney for either 110 (n = 36) or 50 min (n = 44) at pH 7.2, 7.4, or 7.6; pH was changed by varying [HCO3-]; Cai was held constant at approximately 2.5 meq/liter. When citrate was the only substrate available in a Krebs-Ringer-HCO3 perfusate containing 6% substrate-free albumin, both Qcit and Tcit had maximal rates: Qcit much greater than Tcit; at pH 7.6, Qcit and Tcit were significantly reduced below their values at pH 7.2 or 7.4. In contrast to in vivo observations, [citrate]t was not significantly increased at high ECF pH. To test whether [citrate]t in the perfused kidney can increase in alkalosis, 11 additional perfusions were done in the presence of glucose plus lactate plus malate but without added citrate: [citrate]t = 0.6 mumol X g-1 at pH 7.6 and 0.3 mumol X g-1 at pH 7.2 (P less than 0.01); no citrate was detectable in the perfusate, and urinary citrate excretion was negligible. Thus, in the isolated rat kidney, an increase in [citrate]t occurred in alkalosis and was derived from precursors and not from citrate in the ECF. Overall, when only citrate was available to the isolated kidney during alkalosis, a significant rise in [citrate]t did not occur, although Vmax for Tcit and Qcit decreased. These effects of alkalosis on Tcit are consistent with observations in brush-border vesicles, where divalent citrate is the preferential substrate for luminal Na+-coupled transport; by contrast, high ECF pH and [HCO-3] apparently decrease Qcit by a direct effect on the utilization of citrate.

Support of kidney function by long-chain fatty acids derived from renal tissue.

To determine whether the oxidation of long-chain fatty acids (LCFA) derived from renal tissue lipids can support renal function, we perfused isolated rat kidneys with a substrate-free Krebs-Ringer bicarbonate solution containing 6 g/100 ml substrate-free (defatted) albumin. We measured GFR, TNa+, and Qo2 at 7-min intervals from 15 to 99 min after cannulation of the renal artery. Two groups (A and B) of 12 perfusions each were done. During substrate-free perfusion mean %TNa+ was low (A = 45 +/- 2%, B = 62 +/- 5%). When 10(-4) M 2-tetradecylglycidic acid (2-TDGA), a specific and irreversible inhibitor of long-chain acylcarnitine transferase-I, was added to the substrate-free perfusate, significant decreases in %TNa+ (A to approximately 25%; B to approximately 35%) and in Qo2 (delta = -25%) occurred. During perfusion with either 5 mM lactate or 5 mM alpha-ketoglutarate (alpha-KG) %TNa+ increased to approximately 80%. When 2-TDGA was added in the presence of lactate or of alpha-KG no decrease in %TNa+ or Qo2 occurred. Thus, 2-TDGA does not inhibit net renal Na+ transport or O2 uptake in the presence of high concentrations of lactate or alpha-KG, substrates not requiring long-chain acylcarnitine transferase for their utilization. We conclude that oxidation of LCFA released from renal tissue lipids can support a significant portion of Na+ reabsorption.