Caudate nucleus volume and cognitive performance: Are they related in childhood psychopathology?

BACKGROUND: Impaired neuropsychological test performance, especially on tests of executive function and attention, is often seen in children diagnosed with autism spectrum disorders (ASD). Structures involved in fronto-striatal circuitry, such as the caudate nucleus, may support these cognitive abilities. However, few studies have examined caudate volumes specifically in children with ASD, or correlated caudate volumes to cognitive ability. METHODS: Neuropsychological test scores and caudate volumes of children with ASD were compared to those of children with bipolar disorder (BD) and of typically developing (TD) children. The relationship between test performance and caudate volumes was analyzed. RESULTS: The ASD group displayed larger right and left caudate volumes, and modest executive deficits, compared to TD controls. While caudate volume inversely predicted performance on the Wisconsin Card Sorting Test in all participants, it differentially predicted performance on measures of attention across the ASD, BD and TD groups. CONCLUSIONS: Larger caudate volumes were related to impaired problem solving. On a test of attention, larger left caudate volumes predicted increased impulsivity and more omission errors in the ASD group as compared to the TD group, however smaller volume predicted poorer discriminant responding as compared to the BD group.     

Technology assessment of anaesthesia monitors: problems and future directions

Specific factors have limited the interpretation of studies regarding the efficacy, effectiveness and efficiency of technology in anaesthesia. Some of these problems are reviewed, including the lack of specific outcomes necessitating the use of intermediate measures (e.g., hypoxaemia, myocardial ischaemia), which are not necessarily related to ultimate patient outcomes. This emphasizes the need for anaesthesia investigators to define fundamental issues specifically and design studies accordingly. With respect to anaesthesia monitors, the “lead time” or early warning provided by a monitor relative to that required to alter therapy effectively needs to be defined better and compared with the “lead time” without the monitor. After defining the benefit of a monitor, investigators should analyze the cost relative to alternatives (cost-benefit and cost-effectiveness). A hierarchical model to guide technology assessment is presented that addresses in order, the scientific basis of the technology, and the influence on the patient followed by societal issues. Anaesthetists have relied on traditional methods of technology assessment adopted from other disciplines. These methodologies do not address specific issues related to anaesthesia practice (such as “lead time”). In defining problems specific to the specialty of anaesthesia, new outcome measures that focus on the human factors related to decision-making in the operating room need to be developed. Future evaluations of anaesthesia technology require innovative approaches that address specific anaesthesia-related problems. One such approach is the use of simulation-based studies of response patterns to critical incidents.     

Phase II trial of high-dose cisplatin with sodium thiosulfate nephroprotection in patients with advanced carcinoma of the uterine cervix previously untreated with chemotherapy.

Cisplatin is one of the most active single agents in the treatment of advanced cancer of the cervix. The concurrent administration of the nephroprotective agent, sodium thiosulfate, has enabled exploitation of the therapeutic potential of cisplatin. To explore the role of cisplatin dose intensity in the treatment of patients with cancer of the uterine cervix, patients with persistent/recurrent measurable disease were treated with cisplatin at 200 mg/m2 as a 2-hr infusion with sodium thiosulfate given at 3.3 g/m2 1 hr prior to cisplatin and 6.6 g/m2 during the cisplatin infusion. Treatment was repeated monthly. Due to the known cumulative toxicity of cisplatin, treatment beyond two cycles (400 mg/m2) was given only to those patients who had at least demonstrated a PR. Audiologic evaluation was done prior to each cycle of treatment. Eleven patients were entered with a median age of 43 years (range, 25-57), a median KPS of 80% (range, 60-90%), and nine epidermoid and two adenocarcinoma, and all patients had received previous pelvic irradiation. Twenty-eight cycles of treatment were given: 1, five cycles; 3, three cycles; 7, two cycles. No greater than or equal to 3+ hematologic, neurologic, or renal toxicity was demonstrated. Ototoxicity was demonstrated in the mild to moderate hearing loss range (3000-8000 Hz). The greatest threshold shift occurred after the first course of cisplatin. There were three PRs with a maximum duration of 4 months. Due to the significant toxicities encountered, the low response rate, and the limited duration of responses, this trial was closed early to accrual.     

Update on managing hypercholesterolemia. The new NCEP guidelines.

1. The Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATPIII) will significantly increase the number of Americans treated for hypercholesterolemia. 2. The ATPIII focuses on lowering low density lipoprotein cholesterol as a primary initiative and using exercise, diet, and pharmacotherapy as a means for lowering coronary heart disease and risks. 3. The new guidelines list low density lipoprotein cholesterol levels of less than 100 mg/dL as optimal for all clients. 4. The ATPIII places increased attention on high triglyceride levels (> 200 mg/dL) and on early detection and appropriate aggressive treatment for clients at risk for coronary heart disease and events.     

Treatment of Alzheimer’s disease across the spectrum of severity

Alzheimer’s disease (AD) is the most common cause of dementia affecting nearly 18 million people around the world and 4.5 million in the US. It is a progressive neurodegenerative condition that is estimated to dramatically increase in prevalence as the elderly population continues to grow. As the cognitive and neuropsychiatric signs and symptoms of AD progresses in severity over time, affected individuals become increasingly dependent on others for assistance in performing all activities of daily living. The burden of caring for someone affected by the disorder is great and has substantial impact on a family’s emotional, social and financial well-being. In the US, the currently approved medications for the treatment of mild to moderate stages of AD are the cholinesterase inhibitors (ChEIs). Cholinesterase inhibitors have shown modest efficacy in terms of symptomatic improvement and stabilization for periods generally ranging from 6 to 12 months. There are additional data that have emerged, which suggest longer-term benefits. For the moderate to severe stages of AD, memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist is in widespread use and has shown modest benefit as monotherapy and in combination with ChEIs. The cost effectiveness of the currently available therapeutic agents for AD has undergone great scrutiny and remains controversial, especially outside the US. Neuropsychiatric symptoms such as agitation and psychosis are common in AD. Unfortunately, in the US there are no Food and Drug Administration (FDA)-approved agents for the treatment of these symptoms, although atypical antipsychotics have shown some efficacy and have been widely used. However, the use of these agents has recently warranted special caution due to reports of associated adverse effects such as weight gain, hyperlipidemia, glucose intolerance, cerebrovascular events, and an increased risk for death. Alternative agents used to treat neuropsychiatric symptoms include serotonergic antidepressants, benzodiazepines, and anticonvulsant medications.     

Use of Water-Soluble Vitamins in Patients with Chronic Renal. Failure

Little is actually known about the minimum daily requirement for most vitamins in the patient with end-stage renal disease. Many of the studies reviewed suffer from lack of adequate control populations and differing methodologies, making comparisons between these studies difficult. However, patients with renal failure have many restrictions on their dietary intake, frequently suffer from intercurrent illness, and would seem to be at risk for vitamin deficiency. Also, metabolic abnormalities associated with the loss of kidney function may increase the daily requirements for certain vitamins. It is unlikely that dialysis losses of the water-soluble vitamins alone could account for vitamin depletion, and these other factors are likely to play a much more important role. It is of interest to note that the studies which demonstrate little or no vitamin deficiencies are those studies which have been carried out more recently (8, 9, 17). The patients were usually given some vitamin supplementation prior to or during the period of study and thus it is not surprising that most patients failed to demonstrate vitamin deficiency. It is also likely that heightened awareness regarding the propensity for patients with renal failure to develop deficiencies of the water-soluble vitamins has resulted in better dietary instruction and earlier intervention with vitamin supplementation. More efficient dialytic methods have also reduced the restrictions on many foods, and patients are no longer instructed to boil all their fresh vegetables. Although there may be the risk of toxicity when vitamin supplementation is overzealously administered to patients with reduced renal excretory function, it seems prudent to administer some of these water-soluble vitamins to patients with end-stage renal disease who are treated with intermittent dialysis therapy (Table 1). Certainly, this is not a very costly approach. Further studies should be carried out to better evaluate vitamin nutriture in chronically uremic and maintenance dialysis patients and to more rigorously define the minimum dose that would prevent deficiency and avoid toxicity.     

Cisplatin and 5-fluorouracil infusion for metastatic colorectal carcinoma. Differences in survival in two patient groups with similar response rates

Because of reported synergism between 5-fluorouracil (5-FU) and cisplatin (CDDP) in L1210 leukemic mice and activity of this combination in clinical studies, a trial was initiated in previously untreated patients with advanced colorectal carcinoma. Cisplatin at 20 mg/m2 and 5-FU as a continuous infusion at 1000 mg/m2 were both administered for 5 consecutive days every 4 weeks. Forty-one patients were treated at Memorial Sloan-Kettering Cancer Center (MSKCC) and 46 were treated by the Community Clinical Oncology Program (CCOP) physicians. A 50% reduction in measurable disease was seen in 12 of 35 (34%) MSKCC patients and in nine of 41 (22%) of the CCOP patients with 95% confidence intervals of 0.18 to 0.50 and 0.10 to 0.35 in the two groups, respectively. The predominant toxicities were as follows: nausea and vomiting, 32%; mucositis, 26%; leukocyte counts less than 2000 cells/mm3, 17%; platelet counts less than 25,000 cells/mm3, 8%; and severe neurotoxicity, 5%. Dose attenuation was similar in the two groups. The median survival was 16.4 months for the MSKCC group and 9.6 months for the CCOP group (P = 0.0003). Although the baseline characteristics (age, sex, performance status, and baseline lactic dehydrogenase [LDH] and alkaline phosphatase) were similar, on further examination differences between the two groups were evident. In the MSKCC group, 14% of patients with liver metastases had greater than 50% of their liver involved with tumor whereas this occurred in 41% of the CCOP group (P = 0.03). The LDH values greater than 500 U/l were observed in 10% of patients in the MSKCC group and in 37% of the patients in the CCOP group (P = 0.007). Characteristics which reflect the bulk of disease, such as the percent of liver involvement, need to be analyzed in order to evaluate purported survival differences in randomized and nonrandomized trials of colorectal carcinoma.     

Nonablative dermal remodeling with a 585-nm, 350-microsec, flashlamp pulsed dye laser: clinical and ultrastructural analysis.

BACKGROUND: A nonablative 350-microsec, 585-nm, flashlamp pulsed dye laser is currently being used for the treatment of rhytides. OBJECTIVE: To analyze both clinical rhytid improvement and electron microscopic evidence of ultrastructural changes after treatment with a nonablative 350-microsec, 585-nm, flashlamp pulsed dye laser. RESULTS: At 6 months after two treatments, 40% of the treated subjects noted mild improvement in rhytid appearance. Nontreating physician evaluation revealed some degree of improvement in 50% of the treated subjects. Mild improvement in quality and texture of the skin was also reported by 50% of the subjects. Electron microscopic evaluation showed ultrastructural changes that are consistent with new collagen formation. CONCLUSION: Treatment with a nonablative 350-microsec, 585-nm, flashlamp pulsed dye laser can lead to both clinical and electron microscopic evidence of improvement in photo-damaged skin.