A longitudinal neuropsychological study of partial brain radiation in adults with brain tumors.

OBJECTIVE: To investigate longitudinal cognitive functioning in patients with brain tumor treated with modern highly conformal fractionated partial brain radiation therapy (RT). METHODS: Seventeen (of 22 initial consecutive patients) adults with primarily low-grade brain neoplasms who underwent either biopsy or tumor resection were tested at pre-RT baseline and at 3, 6, 12, and 24 months after baseline. Participants were classified as RT-treated nonprogressors (n = 12) or progressors (n = 3) based on serial follow-up structural imaging. Two patients received surgery only and served as controls to help minimize surgical, practice, test form, or other potential non-RT effects. Serial neuropsychological assessments were conducted using alternate forms of the Selective Reminding Test, 10/36 Spatial Recall Test, and Symbol Digit Modality Test (oral, written) as well as the Shipley Scale (baseline only), Wechsler Adult Intelligence Scale-Revised Digit Span, Trail Making Test, and the Symptom Checklist-90-Revised Global Severity Index scale. RESULTS: There was evidence of subtle attention and memory improvement in RT-treated nonprogressors throughout the 2-year period, with no evidence of cognitive decline. In contrast, patients with disease progression evidenced more substantial decline in memory and attention. CONCLUSIONS: Partial brain fractionated RT was not associated with adverse neuropsychological effects through the first 2 years following therapy.

Metastatic adenocarcinoma to a pituitary adenoma.

Metastatic tumor to a pituitary adenoma has rarely been documented in the literature. We report a case of a 60-year-old man who presented with a history of progressive blurred vision and an incomplete homonymous hemianopsia. Magnetic resonance imaging showed a 5 cm heterogeneous mass which focally was contrast enhancing, involving the sella turcica and extending into the right cavernous sinus region. After worsening symptoms, repeat magnetic resonance imaging showed an increase in size of the lesion. Histologically, the mass consisted of a metastatic adenocarcinoma to a nonsecreting pituitary adenoma. The carcinoma stained focally positive with antibodies to carcinoembryonic antigen, cytokeratin 20, and p53 (60% of tumor cells), and did not stain with antibody to cytokeratin 7. The histologic appearance and immunohistochemical profile of the metastasis suggests a colorectal primary.

Multiresidue method for the analysis of pesticide residues in fruits and vegetables by accelerated solvent extraction and capillary gas chromatography.

An analytical procedure using accelerated solvent extraction and capillary gas chromatography with electron capture and flame photometric detections was developed to simultaneously determine residues of different pesticides in fruits and vegetables. Single laboratory validation of the method was carried out for 28 compounds selected from eight pesticide classes, in blank and fortified samples of fresh pear, cantaloupe, white potato, and cabbage. The method had to meet specific established validation criteria for regulatory purposes applicable to our laboratory. At each of the two fortification levels studied, 24 of the 28 pesticides gave recoveries of more than 70% with a coefficient of variation of less than 10%. With respect to existing procedures, the method showed acceptable limits of detection (from 0.0019 to 0.14 microg/g depending on the pesticide and matrix) while minimizing environmental concerns, time, and labor.

High maternal serum inhibin A levels following the loss of one fetus in a twin pregnancy.

Inhibin A levels are elevated in the second trimester of pregnancies affected with fetal Down syndrome, on average, two times the level in unaffected pregnancies. Inhibin A levels are also two times higher in twin than in singleton pregnancies. Prenatal serum screening using inhibin A levels as a second trimester marker began at the Women and Infants Hospital in March 1998. We describe a case of a 17-year-old woman thought to have had a complete spontaneous abortion of a twin pregnancy but later found to be continuing the pregnancy with a single fetus. Routine second trimester prenatal serum screening revealed an extremely elevated inhibin A level of 39 MoM (multiples of the median). The patient delivered an apparently healthy female infant at 41 weeks of gestation. Therefore, inhibin A may be extremely elevated in the second trimester of a twin pregnancy after the loss of one fetus and this increased inhibin A level does not have any obvious adverse maternal or fetal effects.

The effect of integrating substance abuse treatment with prenatal care on birth outcome.

OBJECTIVE: To determine whether engaging pregnant substance abusers in an integrated program of prenatal care and substance abuse treatment would improve neonatal outcomes. STUDY DESIGN: The subjects were women who voluntarily enrolled in Project Link, an intensive outpatient substance abuse treatment program at Women and Infants Hospital, Providence, RI. A total of 87 women received substance abuse treatment in conjunction with their prenatal care; the comparison group of 87 women received equivalent prenatal care but did not enroll in the substance abuse treatment program until after they delivered. The two groups of women were similar demographically and socioeconomically and had similar substance abuse histories. Univariate and multivariate analyses were performed. The key outcomes were gestational age at delivery, birth weight, preterm delivery, Apgar scores, and neonatal intensive care admission rate. Factors controlled in the multivariate models included demographics, socioeconomic status, parity, and prenatal care. RESULTS: Infants born to women who enrolled prenatally were 400 gm heavier (p < 0.001), and their gestational age was 2 weeks longer (p < 0.001) than infants of mothers enrolled postpartum. In addition, they were approximately one-third as likely to be born with a low birth weight (p < 0.01) and approximately one-half as likely to be admitted to the neonatal intensive care unit (p < 0.05). CONCLUSION: Neonatal outcome is significantly improved for infants born to substance abusers who receive substance abuse treatment concurrent with prenatal care compared with infants born to substance abusers who enter treatment postpartum.

Strength training can improve steadiness in persons with essential tremor.

We evaluated the effect of a strength-training program on the ability of persons with essential tremor to exert steady forces with the index finger. Thirteen subjects with a diagnosis of essential tremor were assigned to three different groups: one group trained with heavy loads, one with light loads, and one did not perform any training. Subjects attempted to generate steady contractions during both postural and constant-force tasks. Steadiness was quantified by the root mean square amplitude of acceleration during postural tasks and the standard deviation and coefficient of variation of force during the constant-force tasks. Subjects who performed the training program with heavy loads experienced an increase in steadiness around the target force during the constant-force tasks. Subjects in the other two groups did not exhibit any changes. These findings suggest that strength training can decrease the magnitude of tremor. However, we did not observe any associated improvements in functional abilities.

Effect of subcutaneous recombinant human erythropoietin in cancer patients receiving radiotherapy: final report of a randomized, open-labelled, phase II trial.

The purpose of this study was to determine the safety, efficacy and impact on quality of life of recombinant human erythropoietin (r-HuEPO) for cancer patients undergoing radiotherapy (RT). An open-labelled randomized design was used, with patients randomized to either treatment or control arms. Patients in the treatment arm received r-HuEPO given by subcutaneous injection at a dose of 200 units kg(-1) day(-1) plus oral iron supplements (ferrous sulphate 325 mg p.o. t.i.d.). Entry was restricted to patients with carcinoma of the lung, uterine cervix, prostate or breast who presented for RT with anaemia parameters reflective of 'the anaemia of chronic disease'. Radiotherapy policies (portals, doses, fraction size, etc.) were determined by the site and stage of disease. Complete blood counts (CBCs) were obtained weekly. The target level of haemoglobin was 15 g dl(-1) for men and 14 g dl(-1) for women. Quality of life (QOL) was assessed weekly by using an analogue scale to judge energy, activities of daily living and overall quality of life. Forty-eight patients were entered in the study, 24 in the treatment arm and 24 in the control arm. The prerandomization demographic characteristics and mean laboratory values were comparable in both arms. The mean haemoglobin at completion was 13.6 g dl(-1) for r-HuEPO-treated patients compared with 11.0 g dl(-1) for control subjects (P = 0.0012). Patients who received r-HuEPO demonstrated a mean weekly haemoglobin increase of 0.41 g dl(-1) compared with a decrease in mean haemoglobin level in controls for 6 of the 7 weeks of the study (mean weekly decrease of 0.073 g dl(-1)). Target levels of haemoglobin were achieved by 41.6% of r-HuEPO-treated patients compared with none of the control subjects. The mean platelet count declined in both arms of the study with RT but the decline from pretreatment was less rapid in r-HuEPO-treated patients (11.2% decrease) compared with controls (26.3% decrease) and was statistically significant during weeks 4-6. Toxicity was minor with only mild irritation at the injection site. Mean quality of life end points were superior in the treatment arm but not statistically significant. r-HuEPO had a beneficial effect on weekly haemoglobin levels in patients undergoing RT with response rates similar to other studies. There was also a less rapid decline in weekly platelet counts in r-HuEPO-treated patients compared with control subjects. Further studies are needed to address the optimum dose and scheduling as well as the impact of r-HuEPO on clinical outcomes.

Functional imaging in treatment planning of brain lesions.

PURPOSE: Explore the use of functional imaging data in radiation treatment planning of brain lesions. METHODS AND MATERIALS: Compare the treatment-planning process with and without the use of functional brain imaging for clinical cases where functional studies using either single photon emission computed tomography or magnetic resonance imaging are available. RESULTS: A method to register functional image data with planning image studies is needed for functional treatment planning. Functional volumes are not simply connected regions. One activation study may produce many isolated functional areas. After finding the functional volumes and registering the functional information with the planning imaging data, the tools used for conventional three-dimensional treatment planning are sufficient for functional treatment planning. However, the planning system must provide dose-volume histograms for volumes of interest that consist of isolated pieces. Treatment plans that spare functional brain while providing identical target coverage can be constructed for lesions situated near the functional volume. However, the dose to other areas of the brain may be increased. CONCLUSIONS: Functional imaging will make determination of dose response of eloquent areas of the brain possible when combined with volumetric dose information and neuropsychological evaluation prior to and after radiation therapy. Realizing the full potential of functional imaging studies will require improved delineation of activated volumes and determination of the uncertainties in functional volume delineation. Optimization of treatment plans by minimizing dose to volumes activated during functional imaging studies should be used cautiously, because the dose to "silent," but possibly eloquent, brain may be increased.

Repositioning accuracy of a noninvasive head fixation system for stereotactic radiotherapy.

We report on the repositioning accuracy of patient setup achieved with a noninvasive head fixation device for stereotactic radiotherapy. A custom head mask which attaches to our stereotactic radiosurgery head ring assembly is fabricated for each patient. The position and orientation of a patient in the stereotatic space at the time of treatment are determined from analyzing portal films containing images of radio-opaque spheres embedded in a custom mouthpiece. From analysis of 104 setups of 12 patients, we find that the average distance between the treated isocenter and its mean position is 1.8 mm, and that the standard deviations of the position of the treated isocenter in stereotactic coordinate space about its mean position are less than 1.4 mm in translation in any direction and less than 1 degree of rotation about any axis.

Synthesis and analysis of the enantiomers of calmidazolium, and a 1H NMR demonstration of a chiral interaction with calmodulin.

Calmidazolium [R24571, 1-[bis(4-chlorophenyl)methyl]-3-[2-(2,4-dichlorophenyl)-2-[(2,4- dichlorophenyl)methoxy]ethyl]-1H-imidazolium chloride] is a potent calmodulin inhibitor. This paper describes the synthesis and properties of the enantiomers of calmidazolium from the enantiomers of miconazole [1(N)-(2-(2,4-dichlorobenzyloxy)-2-(2,4 dichlorophenyl))-ethyl imidazole], prepared from the racemate by chiral preparative scale high performance liquid chromatography. Overlap between ligand and protein resonances in the aromatic region of the 1H NMR spectrum of the calmidazolium-calmodulin complexes has been obviated by preparation of the protein with all of its nine phenylalanine rings deuterated (Phe-d5 calmodulin). This has been accomplished by the overexpression of calmodulin derived from Trypanosoma brucei rhodiesiense in E. coli in a medium supplemented with ring-deuterated phenylalanine. The kinetics of binding of each enantiomer are slow on the 1H NMR time scale as judged by the behaviour of the H2 resonance of Histidine-107, which is clearly visible under the sample conditions used. The aromatic spectral regions of the protein-bound (+) and (-) enantiomers contrast strikingly, reflecting differences in bound environment and/or conformation.

Parkinson's disease: managing symptoms and preserving function.

Two strategies of drug therapy for Parkinson's disease (PD) are neuroprotective and symptomatic. In early PD, selegiline may delay need for symptomatic treatment, but whether this represents a delay in disease progression remains controversial. The decision to begin symptomatic therapy depends on how disabling or troublesome symptoms are to the patient. Anticholinergics are often used as monotherapy for alleviation of early tremor. When levodopa is added, it may be reasonable to begin with the controlled-release form. The variety of dopamine agonists used as adjunctive agents is increasing. Research continues on surgical therapies and fetal tissue transplantation.

Clinical evaluation of cervical radiculopathy and myelopathy.

This article considers the entities of cervical radiculopathy and myelopathy. Beginning with a brief historical note and neuroanatomy review of the cord and nerve roots, the discussion proceeds with analysis of symptoms and signs of cervical root disease and then compressive cervical myelopathy. A discussion of diagnostic testing and a differential diagnosis follows. A brief review of conservative medical therapy concludes the article.