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Biomedical subjects

P New

Publications and source records attributed to P New.

13 recordsLinked to original sources

Hypophonia in Parkinson's disease: neural correlates of voice treatment revealed by PET.

OBJECTIVE: To investigate the neural correlates of hypophonia in individuals with idiopathic PD (IPD) before and after voice treatment with the Lee Silverman Voice Treatment method (VT) using (15)O-H(2)O PET. METHODS: Regional cerebral blood flow (rCBF) changes associated with overt speech-motor tasks relative to the resting state were measured in the IPD subjects before and after VT, and in a group of healthy control volunteers. RESULTS: Behavioral measures of voice loudness significantly improved following treatment. Before VT, patients had strong speech-related activations in motor and premotor cortex (M1-mouth, supplementary motor cortex [SMA], and inferior lateral premotor cortex [ILPm]), which were significantly reduced post-VT. Similar to the post-treatment session, premotor activations were absent (SMA) or below statistical threshold (M1-mouth) in the healthy control group. In addition, following VT treatment, significant right-sided activations were present in anterior insular cortex, caudate head, putamen, and dorsolateral prefrontal cortex (DLPFC). Finally, the VT-induced neural changes were not present with transient experimenter-cued increases of loudness in VT-untreated patients. CONCLUSIONS: Effective improvement of IPD hypophonia following voice treatment with VT was accompanied by a reduction of cortical motor-premotor activations, resembling the functional pattern observed in healthy volunteers and suggesting normalization, and additional recruitment of right anterior insula, caudate head, putamen, and DLPFC. This treatment-dependent functional reorganization suggests a shift from an abnormally effortful (premotor cortex) to a more automatic (basal ganglia, anterior insula) implementation of speech-motor actions.

Aged↗

Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine.

DepoCyte is a slow-release formulation of cytarabine designed for intrathecal administration. The goal of this multi-centre cohort study was to determine the safety and efficacy of DepoCyte for the intrathecal treatment of neoplastic meningitis due to breast cancer. DepoCyte 50 mg was injected once every 2 weeks for one month of induction therapy; responding patients were treated with an additional 3 months of consolidation therapy. All patients had metastatic breast cancer and a positive CSF cytology or neurologic findings characteristic of neoplastic meningitis. The median number of DepoCyte doses was 3, and 85% of patients completed the planned 1 month induction. Median follow up is currently 19 months. The primary endpoint was response, defined as conversion of the CSF cytology from positive to negative at all sites known to be positive, and the absence of neurologic progression at the time the cytologic conversion was documented. The response rate among the 43 evaluable patients was 28% (CI 95%: 14-41%); the intent-to-treat response rate was 21% (CI 95%: 12-34%). Median time to neurologic progression was 49 days (range 1-515(+)); median survival was 88 days (range 1-515(+)), and 1 year survival is projected to be 19%. The major adverse events were headache and arachnoiditis. When drug-related, these were largely of low grade, transient and reversible. Headache occurred on 11% of cycles; 90% were grade 1 or 2. Arachnoiditis occurred on 19% of cycles; 88% were grade 1 or 2. DepoCyte demonstrated activity in neoplastic meningitis due to breast cancer that is comparable to results reported with conventional intrathecal agents. However, this activity was achieved with one fourth as many intrathecal injections as typically required in conventional therapy. The every 2 week dose schedule is a major advantage for both patients and physicians.

Adult↗

Radiation injury to the nervous system.

This article reviews the current knowledge with regard to neurotoxicity of conventional radiation, including recent understanding of the pathophysiology, molecular biology, diagnostic evaluation and clinical presentations, as well as proposed treatment modalities and possible protective agents.

Brain↗

Language mapping in pretreatment planning of patients with cerebral arteriovenous malformation: a PET study.

PURPOSE: Three patients who had cerebral arteriovenous malformations underwent language mapping by positron emission tomography (PET) to identify the dominant hemisphere for language and the spatial relation of lesions to language areas. METHODS: Mapping was performed to assess the risk that surgery could cause neurologic deficits and to plan other therapeutic strategies. RESULTS: The information obtained by PET language mapping changed the course of management for these patients. Two patients were treated with stereotactic radiosurgery and one patient with surgical resection. CONCLUSIONS: PET imaging can be a valuable noninvasive tool for mapping the functional cortex and for preoperative planning of different treatment options in patients with arteriovenous malformations.

Adolescent↗

FDG positron emission tomography in diffuse Lewy body disease: a case report.

Lewy body disease is a clinicopathologic condition that includes Parkinson's disease at one end and diffuse Lewy body disease at the other hand. The latter is often associated with progressive cognitive deterioration, levodopa-responsive parkinsonism, fluctuations of cognitive and motor functions, and visual and auditory hallucinations. In addition, it can be a familial disease. Clinical and positron emission tomographic findings are described in a patient with atypical dementia and movement disorder and a pathologically proved diagnosis of diffuse Lewy body disease.

Brain↗

A phase I and pharmacokinetic trial of terephthalamidine (NSC 57155) as a 120-hour continuous infusion.

In this phase I study, terephthalamidine was administered as a 120-hour continuous infusion repeated every 21 days. Thirteen patients received 27 courses of terephthalamidine at four dose levels ( 14, 28, 46, and 70 mg/m2/day). Dose-limiting toxicity consisted of profound and intractable anorexia, weight loss and prostration in all patients. Toxicity was delayed and accompanied by hyponatremia and hypokalemia. No hematologic or other toxicity was documented. One patient with adenocarcinoma of the lung had a 40% decrease in mediastinal lymph nodes and resolution of a pleural effusion lasting 2 months. Pharmacokinetic analysis by HPLC was performed in all patients during their first course. The harmonic mean terminal half-life for terephthalamidine was 23 hours with a plasma clearance of 1.7 1/hr/m2. Both plasma concentrations achieved during infusion (r2 = 0.9) and area under the curve (AUC) (r2 = 0.8) were proportional to increase in dose (p < 0.002). Renal excretion accounted for 64% of the total cumulative dose, with an average renal clearance of 1.16 1/hr/m2. Due to the unacceptable toxicity seen at all doses with this schedule, no further studies are recommended unless the mechanism of toxicity is better understood and can be prevented.

Adult↗

Long-term response to crisnatol mesylate in patients with glioma.

A total of 26 patients (6 with anaplastic astrocytoma; 20 with glioblastoma) were treated with crisnatol mesylate. All patients had residual or progressive disease following surgery and standard radiotherapy; nine patients had prior chemotherapy. Crisnatol was administered as a 72-hour infusion every 21 days at a starting dose of 2250 mg/m2. Two patients who had not received prior chemotherapy achieved a complete response and remain in continuous complete remission over seven and six years, respectively, post-diagnosis. Two other patients remained stable on crisnatol for 10 months before disease progression. One patient with mixed oligodendroglioma/glioblastoma progressed after 12 months on crisnatol. He survives at 7 years post-diagnosis, with Karnofsky Performance Status of 60 following other therapies. One patient with anaplastic astrocytoma stopped treatment by request after 10 months and remains stable 64 months post diagnosis. Seventeen evaluable patients, including nine patients with prior chemotherapy, progressed after 2-9 courses of therapy. Median survival is 9.25 months, with a one year survival rate of 30% and 2 years survival rate of 17%. Neurotoxicity was acute and dose-limiting. Side effects were tolerable and limited to duration of infusion. Two complete, long-lasting responses to crisnatol mesylate in patients with progressive malignant glioma are encouraging results and warrant further investigation.

Adult↗

Taxol neuropathy. Electrodiagnostic and sural nerve biopsy findings.

Taxol has recently been approved for the treatment of ovarian cancer that has failed to respond to other chemotherapeutic agents. A predominantly sensory neuropathy has been reported in patients receiving taxol, but corresponding nerve changes have not been described. The patient described herein received taxol at a dose of 275 mg/m2 every 21 days. The sural nerve biopsy performed after 17 courses of taxol (cumulative dose, 6603 mg) showed severe nerve fiber loss, axonal atrophy, and secondary demyelination. Axonal regeneration was absent. The findings are compatible with a cell body disease or a length-dependent, distal neuropathy with failure of axonal regeneration. The findings observed in taxol-induced neuropathy are important to document for comparison with other neoplastic and paraneoplastic neuropathies affecting patients with cancer.

Electrodiagnosis↗

Phase I clinical trial of ormaplatin (tetraplatin, NSC 363812).

Ormaplatin is a platinum analog that was developed because of an altered toxicity profile and non-cross resistance to cisplatin in both in vitro and in vivo models. To determine the toxicities and maximum tolerated dose of ormaplatin on a daily times five schedule, patients with refractory solid tumors received ormaplatin on five consecutive days at nine dose levels ranging from 1.0 to 15.0 mg/m2/day. A total of 35 patients received 70 cycles of therapy. Nausea and vomiting and myelosuppression were moderate and not dose-limiting. Dose-limiting neurotoxicity, consisting of a sensory peripheral neuropathy, was seen in all five patients who received cumulative doses greater than or equal to 165 mg/m2. This neurotoxicity was symptomatic in all patients and caused significant functional impairment in four patients with inability to walk in two patients. A sensitive atomic absorption spectroscopy analysis performed for one patient at the 13.0 mg/m2/day dose level showed a Cpmax of 163 ng/ml and a t1/2 of 10.9 min for free platinum. A phase II dose could not be determined due to the onset of peripheral neuropathy at low cumulative doses and not at absolute dose levels.

Adult↗

Patient-controlled analgesia for chronic cancer pain in the ambulatory setting: a report of 117 patients.

Patient-controlled analgesia (PCA) represents a drug-delivery system in which patients self-administer predetermined doses of opiate analgesics. We have taken advantage of recent advances in pump technology and developed a system in which patients with severe pain received a continuous narcotic infusion, along with the capability of PCA bolus for breakthrough pain. All patients were experiencing chronic pain related to cancer and were unable to obtain adequate pain control with either intermittent parenteral, oral, or rectal narcotics. Sixty-nine percent of patients were treated in the home setting, and the majority received morphine sulfate subcutaneously (SQ). Admixture stability studies using high-pressure liquid chromatography (HPLC) showed that dexamethasone, metoclopramide, and haloperidol could be added to the morphine solutions and remain stable for 1 week at room temperature. Of 117 patients entered, 95% received excellent pain control, and side effects were rare, consisting of subcutaneous needle site infection and respiratory depression. Progressive pain due to either advancing disease or development of drug tolerance could be controlled by increasing opiate infusion rates. We conclude that (1) continuous infusion opiate with PCA bolus capability can be initiated and administered safely in the home setting; (2) patients with pain related to malignancy can be managed well with this system; and (3) pain control programs can be designed, implemented, and evaluated in the private practice setting.

Adult↗