Effects of age on the glucose metabolic changes in mild cognitive impairment.

BACKGROUND AND PURPOSE: Decreased glucose metabolism in the temporal and parietal lobes on FDG-PET is recognized as an early imaging marker for the AD pathology. Our objective was to investigate the effects of age on FDG-PET findings in aMCI. MATERIALS AND METHODS: Twenty-five patients with aMCI at 55-86 years of age (median = 73 years) and 25 age- and sex-matched CN subjects underwent FDG-PET. SPM5 was used to compare the FDG uptake in patients in aMCI-old (>73 years) and aMCI-young (

Spontaneous breathing during partial liquid ventilation in animals with meconium aspiration.

Partial liquid ventilation (PLV) has been shown to improve gas exchange in paralyzed animals and humans with lung disease. The present study tests the hypothesis that PLV improves gas exchange in spontaneously breathing animals with meconium aspiration supported by proportional assist ventilation. Twenty-five adult anesthetized intubated rabbits with experimental meconium aspiration were randomized to gas ventilation (GV) or PLV while being supported by proportional assist ventilation. Minute ventilation, tidal volume, respiratory rate, mean airway pressure, heart rate, and mean arterial and pulmonary arterial pressure were recorded continuously. Every 30 min, arterial blood gases were obtained, and lung compliance, airway resistance, work of breathing, and cardiac output were measured. Animals were sacrificed after 5 h to obtain lung histology. More PLV animals survived until the end of the study period. PaO(2) (14.5 +/- 4.5 versus 25.6 +/- 6.7 kPa; p < 0.01; GV versus PLV) and lung compliance (4.3 +/- 0.4 versus 6.1 +/- 1.2 mL.kPa(-1).kg(-1); p < 0.001) were improved during PLV, resulting in a lower work of breathing (5.3 +/- 2.8 versus 3.5 +/- 1.5 mL.kPa.kg(-1); p < 0.05) and less need for ventilatory support. Minute ventilation and respiratory rate were higher during GV versus PLV, resulting in a slightly lower PaCO(2) (3.9 +/- 0.5 versus 4.5 +/- 0.7 kPa; p < 0.05). Histologic evaluation showed more atelectasis, inflammatory changes, and hemorrhage in GV animals. Other parameters measured were similar. We conclude that PLV improves oxygenation, lung compliance, and survival and results in less lung injury in spontaneously breathing animals with meconium aspiration when supported by proportional assist ventilation.

Efficacy of tracheal gas insufflation in spontaneously breathing sheep with lung injury.

Tracheal gas insufflation (TGI) decreases dead space (V D) and can be combined with continuous positive airway pressure (CPAP) to decrease minute volume (VE) and effort of breathing. In 11 anesthetized sheep, we induced acute lung injury (ALI) through oleic acid (OA) infusion and studied the effects of TGI combined with CPAP (CPAP-TGI) at different TGI flows and with catheters of different designs. Sheep were randomized to two groups: Group A (n = 7) was placed on CPAP and CPAP-TGI at 10 and 15 L/min of insufflation flow delivered through a reverse thrust catheter (RTC). Group B (n = 4) was placed on CPAP and CPAP-TGI at a flow of 10 L/min delivered through a RTC, and through a straight flow catheter (SFC). Compared with CPAP alone, CPAP-TGI resulted in significantly lower VD, VE, pressure time product, and work of breathing. We found no additional benefit from TGI flow of 15 L/min, compared with 10 L/min, and no statistically significant difference between the SFC and the RTC. In conclusion, TGI can be combined with CPAP in this model of ALI to reduce ventilation and effort of breathing.

Teaching multiplication facts to students with learning disabilities.

Multiple baseline designs were used to examine the effects of an instructional package on accuracy of performance in solving multiplication facts by 3 students with learning disabilities. The instructional package included the following components: (a) a modified instructional sequence in which multiplication facts were grouped into the zeros, ones, doubles, fives, and nines categories, and those remaining; (b) identification of the category in which each fact belonged; (c) mnemonic strategies associated with solving facts in each category; and (d) steps to be completed for solving facts in each category. Results indicated that the instructional package produced substantial and immediate effects. After receiving instruction, a participant's accuracy was often 100%, and this was maintained throughout the evaluation even as other strategies were introduced. Comparable results occurred across students, demonstrating replication of the effects of the instructional package.

A randomized trial of a nonabsorbable antibiotic lozenge given to alleviate radiation-induced mucositis.

BACKGROUND: The objective of this study was to determine whether a nonabsorbable antibiotic lozenge could alleviate radiation-induced oral mucositis. METHODS: Patients scheduled to receive radiation therapy to more than one-third of the oral cavity mucosa were selected for the study. After stratification, patients were randomized to receive either a nonabsorbable antibiotic lozenge or a placebo. Both groups were then evaluated for mucositis by health care providers and self-report instruments. RESULTS: Fifty-four patients were randomized to receive the antibiotic lozenge and 58 to receive the placebo. There were no substantial differences or trends in mucositis scores between the two study arms as measured by the health care providers. However, the mean patient-reported mucositis score and the duration of patient-reported Grade 3-4 mucositis were both lower in the patients randomized to the antibiotic lozenge arm (P = 0.02 and 0.007, respectively). CONCLUSIONS: This prospective, controlled trial provides evidence to suggest that a nonabsorbable antibiotic lozenge can decrease patient-reported radiation-induced oral mucositis to a modest degree. Nonetheless, this evidence does not appear to be compelling enough to recommend this treatment as part of standard practice.

Placebo-controlled trial of sucralfate for inhibiting radiation-induced esophagitis.

PURPOSE: To determine whether a sucralfate oral solution can prevent/alleviate radiation-induced esophagitis. PATIENTS AND METHODS: Patients included on this clinical trial were beginning thoracic radiation therapy to the mediastinum. Following stratification, they were randomized, in a double-blind manner, to receive a sucralfate solution or an identical-appearing placebo solution. Esophagitis was measured by physicians who used standard criteria and also by patients who used short questionnaires completed weekly during the course of the trial. RESULTS: A total of 97 assessable patients were entered onto this clinical trial. During the first 2 weeks of the study, two placebo patients (4%) stopped their study medication, compared with 20 sucralfate patients (40%). This was related to substantially increased incidences of gastrointestinal toxicity (58% of sucralfate patients v 14% of placebo patients; P > .0001). There was no substantial benefit from the sucralfate in terms of esophagitis scores. CONCLUSION: This oral sucralfate solution does not appear to inhibit radiation-induced esophagitis and is associated with disagreeable gastrointestinal side effects in this patient population.

Neurotensin, N-acetyl-aspartylglutamate and beta-endorphin modulate [3H]dopamine release from guinea pig nucleus accumbens, prefrontal cortex and caudate-putamen.

Dopaminergic hyperactivity in nucleus accumbens and dopaminergic hypoactivity in prefrontal cortex are thought to underlie positive and negative symptoms of schizophrenia, respectively. The caudate putamen is the neuroanatomical substrate for extrapyramidal side effects resulting from chronic antipsychotic treatment. We sought to identify potential endogenous regulators of dopamine release that might produce differential effects in these brain areas. We tested neurotensin, N-acetyl-aspartyl-glutamate and beta-endorphin for potential regulation of [3H]dopamine release in these regions of guinea pig brain. All three peptides stimulated dopamine release, above basal activity, at all concentrations tested in the three regions. Neurotensin significantly enhanced and N-acetyl-aspartyl-glutamate had no significant effect on N-methyl-D-aspartate-stimulated release from all three regions. In contrast, beta-endorphin significantly inhibited N-methyl-D-aspartate-stimulated release in nucleus accumbens and caudate putamen. These results suggest that these neuropeptides may regulate endogenous dopamine release and therefore may be potential therapeutic targets for antipsychotic drug development.

Regulation of [3H] dopamine release from mesolimbic and mesocortical areas of guinea pig brain by sigma receptors.

The role of sigma (sigma) receptors in brain function is poorly defined. They are located in limbic areas, including nucleus accumbens (NAC) and prefrontal cortex (PFC), both of which are thought to be involved in schizophrenia. Many antipsychotics (APs), including haloperidol, bind with high affinity to sigma receptors. Dopaminergic hyperactivity in NAC is thought to underlie positive symptoms of schizophrenia, while dopaminergic hypoactivity in PFC is thought to underlie negative symptoms. Sigma receptors regulate N-methyl-D-aspartate (NMDA)-stimulated [3H] dopamine ([3H]DA) release in caudate-putamen (CP), the neuroanatomical substrate for extrapyramidal side effects resulting from chronic AP treatment. In the current study, we investigated whether sigma receptors could similarly regulate DA release in mesolimbic and mesocortical tissue, and the relative participation of different sigma receptor subtypes in this process. We found that, in NAC, regulation of DA release by the prototypical sigma agonist (+)pentazocine was mediated predominantly by the sigma 1 receptor, whereas in the PFC a portion of the (+)pentazocine effect was likely mediated by the sigma 2 receptor. We also observed, in both the NAC and PFC, that regulation of DA release by the sigma agonist BD737 was mediated primarily by the sigma 1 receptor. In addition, we determined that (+)pentazocine or BD737 effects on DA release were not mediated via opioid receptors, nor the phencyclidine (PCP) binding site within the NMDA receptor-operated cation channel, nor by sigma receptor effects upon [3H]DA accumulated by noradrenergic terminals in PFC.

Olsalazine is contraindicated during pelvic radiation therapy: results of a double-blind, randomized clinical trial.

PURPOSE: A randomized clinical trial from Great Britain suggested a possible beneficial effect of acetylsalicylate in the prevention of radiation-induced bowel toxicity. Olsalazine is an orally administered drug designed to deliver 5-aminosalicylate to the large bowel with minimal systemic absorption. A randomized clinical trial was undertaken to assess the effectiveness of olsalazine in preventing acute diarrhea in patients receiving pelvic radiation therapy. METHODS AND MATERIALS: Patients receiving pelvic radiation therapy were randomized, in double-blind fashion, to olsalazine 250 mg, two capsules twice daily, or an identical appearing placebo, two capsules twice daily. Patients were then evaluated weekly during radiation therapy for the primary study endpoint, diarrhea, as well as rectal bleeding, abdominal cramping, and tenesmus. RESULTS: The study was closed early, after entry of 58 evaluable patients, when a preliminary analysis showed excessive diarrhea in patients randomized to olsalazine. The incidence and severity of diarrhea were worse in patients randomized to olsalazine (p = 0.0036). Sixty percent of the patients randomized to olsalazine experienced Grade 3 or 4 diarrhea compared to only 14% randomized to placebo. There was also a trend toward higher incidence and greater severity of abdominal cramping in patients who were randomized to olsalazine (p = 0.084). CONCLUSION: Administration of olsalazine during pelvic radiation therapy resulted in an increased incidence and severity of diarrhea. Olsalazine is contraindicated in patients receiving pelvic radiation therapy.

Randomized trial of a chlorhexidine mouthwash for alleviation of radiation-induced mucositis.

PURPOSE: To determine whether a chlorhexidine mouthwash could alleviate radiation-induced oral mucositis. PATIENTS AND METHODS: Patients scheduled to receive radiation therapy to include greater than one third of the oral cavity mucosa were selected for study. Following stratification, they were randomized in a double-blind manner to receive a chlorhexidine mouthwash or a placebo mouthwash. Both groups were then similarly evaluated for mucositis and mouthwash toxicity. RESULTS: Twenty-five patients were randomized to receive the chlorhexidine mouthwash, while 27 received the placebo mouthwash. Treatment arms were well balanced. There was a trend for more mucositis and there was substantially more toxicity (eg, mouthwash-induced discomfort, taste alteration, and teeth staining) on the chlorhexidine arm. CONCLUSION: In contrast to the prestudy hypothesis that a chlorhexidine mouthwash might provide benefit for patients receiving radiation therapy to the oral mucosa, this study provides strong evidence suggesting that a chlorhexidine mouthwash is detrimental in this clinical situation.

Adult adjustment among high school graduates with mild disabilities.

This study investigated the adult adjustment of a statewide random sample of 737 young adults with learning disabilities, 59 labeled behaviorally disordered, and 142 labeled mentally disabled, all graduates of special education resource teacher programs. Results are reported in terms of (a) general status information, such as marital status and living arrangements; (b) information about those competitively employed, such as wages, hours worked per week, and percentage of living expenses paid; and (c) comparison of competitively employed versus unemployed individuals, in terms of high school vocational training and work experiences. Information is also provided on postsecondary education and overall "successful" adult adjustment. Data are compared across disability groups and across gender, where relevant.

Complex partial status epilepticus in a patient with dural metastases.

We describe a 68-year-old man with invasive transitional cell carcinoma of the bladder metastatic to the dura who presented with complex partial status epilepticus (CPSE). To our knowledge, the association of CPSE and dural metastases has not been previously reported.

Pilot study of accelerated hyperfractionated thoracic radiation therapy in patients with unresectable stage III non-small cell lung carcinoma.

BACKGROUND: The primary goal of this study was to determine the incidence of severe or greater acute radiation toxicity, and secondarily, response, survival, and local control in patients with unresectable Stage IIIA or B non-small cell lung cancer treated with accelerated hyperfractionated thoracic radiation therapy (AHTRT). METHODS: From September, 1989 through March, 1990, 21 evaluable patients with unresectable Stage IIIA or B non-small cell lung cancer were treated with AHTRT, using 6000 cGy in 40 fractions of 150 cGy twice daily, 6 hours between fractions, with a 2-week break midway through treatment. RESULTS: Two patients (9.5%) had acute Grade 3 radiation esophagitis requiring intravenous hydration, and two patients (9.5%) had acute Grade 3 radiation pneumonitis requiring oxygen and steroids. Only one patient had chronic toxicity, a Grade 3 radiation pneumonitis. Five patients (24%) achieved a complete response, whereas eight (38%) had a partial response or regression. With minimum follow-up of nearly 3 years, 3 patients are alive and 18 are dead. The median survival time and 1-, 2-, and 3-year survival rates were 10.8 months, 48%, 29%, and 14%, respectively. Local control was achieved in 11 of 21 (52%) patients. CONCLUSIONS: This AHTRT regimen can be given with an acceptable incidence of acute radiation toxicity. Response, survival, and local control rates in this unfavorable group of patients are encouraging. A North Central Cancer Treatment Group Phase III study of standard thoracic radiation therapy (6000 cGy in 30 fractions of 200 cGy daily) versus AHTRT (+/- chemotherapy) is now open.

Solitary pulmonary nodules: detection of malignancy with PET with 2-[F-18]-fluoro-2-deoxy-D-glucose.

It is estimated that nearly one-third of solitary pulmonary nodules (SPNs) may represent bronchogenic carcinoma. The noninvasive imaging methods used currently (ie, plain radiography, computed tomography) are not reliable for accurate detection of malignancy in most SPNs. The authors prospectively evaluated use of positron emission tomography (PET) with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) for identification of malignancy in 20 patients with noncalcific, radiographically indeterminate SPNs. PET-FDG imaging demonstrated focal hypermetabolism in 13 biopsy-proved malignant nodules, whereas no increased FDG uptake was seen in the seven benign SPNs. Semiquantitative analysis with computation of differential uptake ratios also helped clearly differentiate benign nodules (mean +/- standard deviation, 0.56 +/- 0.27) from malignant nodules (mean +/- standard deviation, 5.63 +/- 2.38) (P less than .001). Thus, PET-FDG imaging may be a potentially useful noninvasive technique for accurate differentiation of benign and malignant SPNs that are radiographically indeterminate.

Standardization of dosimetry chart checks.

This paper reports on a standardized report form that can be used to analyze dose error rates from radiation therapy. An error classification scheme of Types 1 to 5 was developed to indicate increasing severity of errors. Type 1 (charting errors) and Type 3 (daily dose errors) were the most prominent types. Dosimetry errors were reduced by using the results of the reports to correct operating procedures. Type 1 error rates decreased from 17% initially to an average of 3.9%. An average error rate of 1.7% for Type 3 dose errors was found to be consistent with normal operation. Use of the report form is useful in documenting and correcting errors and as a reporting record for use in a quality assurance program.

Primary lymphoma of bone.

Primary lymphoma of bone is a rare clinical entity that accounts for less than one per cent of all non-Hodgkin's lymphomas. Although they occasionally present as a solitary lesion in bone, lymphoma involving bone is a manifestation of disseminated disease in many instances. All patients initially found to have a solitary lymphoma of bone need to be thoroughly investigated for systemic disease because more than half of the patients presenting with initially solitary bone lesions are found to have systemic disease involving lymph nodes and/or other organs. Choice of therapeutic management is based on the stage of disease. Stage I-E primary lymphoma of bone can be controlled in 70-90% of cases using local radiation therapy alone if adequate radiation doses are used. Patients with advanced disease should be treated with combination chemotherapy in addition to local radiotherapy. Loeffler et al reported long-term survival results of 90% 8-year actuarial overall survival rate for children with primary lymphoma of bone who received combined therapy with radiation and chemotherapy (adriamycin, prednisone and oncovin). The actuarial lymphoma-free survival rate was 100% at eight years. Regardless of stage of the disease, radiation treatment to the primary tumor appears to be critical for adequate local control of disease as well as rapid symptomatic relief.

Spinal cord compression--an oncologic emergency.

Spinal cord compression secondary to epidural metastatic tumor is an emergency clinical situation that requires prompt diagnosis and treatment if permanent neurologic damage is to be prevented. Physicians caring for patients with cancer must maintain a high index of suspicion for this problem. Back pain is a common clinical situation in the general population but in the cancer patient, one should consider this sign indicative of possible spinal cord compression even though a long tumor-free interval has occurred since the original diagnosis of neoplasm. The diagnosis is established by thorough neurologic examination, plain x-rays, myelography, CT and MRI scanning. Once the diagnosis is established, treatment is instituted with steroids, decompressive surgery and postoperative irradiation or external irradiation alone depending upon the emergent nature of the clinical situation. Regardless of the initial treatment, patients with spinal cord compression require management in a multi-disciplinary fashion. Early therapy will result in the best relief of symptoms and maintenance of the ability to walk. The ultimate prognosis of such patients is very dismal in view of the metastatic nature of their disease but prompt diagnosis and treatment is necessary to prevent devastating sequelae for the patients and their families.