Neuropsychological assessment, neuroimaging, and neuropsychiatric evaluation in pediatric and adult patients with sickle cell disease (SCD)

Traditionally, neuropsychological deficits due to Sickle Cell Disease (SCD) have been understudied in adults. We have begun to suspect, however, that symptomatic and asymptomatic Cerebrovascular Events (CVE) may account for an alarming number of deficits in this population. In the current brief review, we critically evaluated the pediatric and adult literatures on the neurocognitive effects of SCD. We highlighted the studies that have been published on this topic and posit that early detection of CVE via neurocognitive testing, neuropsychiatric evaluations, and neuroimaging may significantly reduce adult cognitive and functional morbidities.     

RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature

During the past decade, RGD-peptides have become a popular tool for the targeting of drugs and imaging agents to alphavbeta3-integrin expressing tumour vasculature. RGD-peptides have been introduced by recombinant means into therapeutic proteins and viruses. Chemical means have been applied to couple RGD-peptides and RGD-mimetics to liposomes, polymers, peptides, small molecule drugs and radiotracers. Some of these products show impressive results in preclinical animal models and a RGD targeted radiotracer has already successfully been tested in humans for the visualization of alphavbeta3-integrin, which demonstrates the feasibility of this approach. This review will summarize the structural requirements for RGD-peptides and RGD-mimetics as ligands for alphavbeta3. We will show how they have been introduced in the various types of constructs by chemical and recombinant techniques. The importance of multivalent RGD-constructs for high affinity binding and internalization will be highlighted. Furthermore the in vitro and in vivo efficacy of RGD-targeted therapeutics and diagnostics reported in recent years will be reviewed.     

Long-term follow-up and the role of surgery in adolescents with morbid obesity

PURPOSE: Obesity has become a health-care crisis in the United States. Adolescent obesity is now one of the most common childhood disorders, with 4.7 million American adolescents having a body mass index (BMI) greater than the 95th percentile. Most patients do not respond to diet modification or exercise programs and attention is now turning toward surgery as a source of weight loss in adolescents. Few studies have looked at the overall morbidity and mortality of weight loss surgery in this patient population. METHODS: This is a retrospective study of medical charts of 15 bariatric surgical procedures performed on 14 adolescents without known genetic syndromes associated with severe childhood obesity from 1971 to 2001 at the University of Minnesota. Procedures performed on these patients included vertical banded gastroplasty (n = 7), Roux-en-Y gastric bypass (n = 5), and jejunoileal bypass (n = 3). Jejunoileal bypass procedures were performed from 1971 to 1977, after which time this procedure was abandoned. Patient age ranged from 13 to 17 years (mean, 15.7 years). Mean follow-up time was 6 years, with 9 patients available for long-term follow-up. RESULTS: All procedures were performed using an open technique by 1 surgeon. There were no perioperative deaths; complications included 1 case of wound infection, 2 episodes of dumping syndrome that resolved without revision, 1 episode of hypoglycemia, and 1 case of short-term electrolyte imbalance in a patient who underwent jejunoileal bypass. The average BMI dropped from 58.5 +/- 13.7 to 32.1 +/- 9.7 kg/m(2) (P < .01)--a 45% reduction. CONCLUSIONS: Surgery for morbid obesity is safe and results in significant weight loss in adolescents who fail medical therapy.     

Clustering of dietary variables and other lifestyle factors (Dutch Nutritional Surveillance System).

STUDY OBJECTIVE--The aim was to investigate whether dietary factors cluster in a favourable or unfavourable way and to characterise the groups identified by lifestyle and sociodemographic variables. DESIGN AND SETTING--This cross sectional study was based on data of the 1987-1988 Dutch national food consumption survey (DNFCS), obtained from a panel by a stratified probability sample of the non-institutionalised Dutch population. PARTICIPANTS--3781 adults (1802 males and 1979 females) of the DNFCS, aged 19 to 85 years, were studied. MEASUREMENTS AND MAIN RESULTS--To estimate dietary intake two day food records were used. Lifestyle factors were collected by structured questionnaire and sociodemographic variables were available from panel information. Cluster analysis was used to classify subjects into groups based on similarities in dietary variables. Subsequently, these groups were characterised by sociodemographic and lifestyle factors as well as by the consumption of food groups. Eight clusters were found. In comparison with the guidelines, the dietary quality in four clusters was poor. The cluster with the poorest dietary intake (high intake of fat, cholesterol, and alcohol; low intake of dietary fibre) showed on average a high consumption of animal products (except milk), fats and oils, snacks, and alcoholic beverages, and a low consumption of fruit, potatoes, vegetables, and sugar rich products. Smoking, body mass index, dietary regimen on own initiative, hours of sleep, gender, age, socioeconomic status, and day of the week were found to discriminate among the clusters. CONCLUSIONS--Cluster analysis resulted in substantial differences in mean nutrient intake and seems useful for dietary risk group identification. Undesirable lifestyle habits were interrelated in some clusters, but an exclusive lifestyle for health risk has not been found.     

Home-based Health Risk Appraisal and screening program

In an effort to improve Health Risk Appraisals and to induce individuals to change their lifestyles, comprehensive evaluations and counseling sessions were carried out for 476 participants of an experimental preventive care program (1984). Nurse practitioners interviewed participants in their homes and collected information about their lifestyle, medical history, and family history. In addition, physical examinations were performed and blood samples were obtained for laboratory analysis. This information was used to formulate health risk profiles for all participants who were then counseled on how to decrease identified health risks. Interventions included education about health risks and specific programs which were administered to help modify high-risk behaviors. At one year follow-up, significant risk reductions were reported in many areas of increased risk.Victor W. Acquista, M.D., is a Fellow in General Internal Medicine, Rhode Island Hospital. Tom J. Wachtel, M.D., is Director, Medical Primary Care Unit, Rhode Island Hospital, and Assistant Professor of Community Health, Brown University. Celia I. Gomes, M.P.H., is Health Education Coordinator, Blue Cross/Blue Shield of Rhode Island. Michael Salzillo, M.S., is Team Leader, Statistical Analysis Department, Blue Cross/Blue Shield of Rhode Island. Melanie Stockman, R.N., is Director of Ambulatory Nursing, Rhode Island Hospital.     

Laboratory diagnosis of Mycoplasma pneumoniae infection. 2. Comparison of methods for the direct detection of specific antigen or nucleic acid sequences in respiratory exudates

The efficiency of the direct detection of Mycoplasma pneumoniae in respiratory exudates by an antigen capture, indirect enzyme immunoassay (Ag-EIA), has been compared with its detection with a cDNA probe ('Gen-Probe assay') directed against the specific ribosomal RNA sequences of the organism ('Mycoplasma pneumoniae Rapid Diagnostic System', Gen-Probe, San Diego, California). Both assays showed excellent specificity against a range of mycoplasma species suspended in negative nasopharyngeal aspirates; only M. pneumoniae and M. genitalium reacted. In experiments with graded doses of viable M. pneumoniae cells suspended in negative nasopharyngeal aspirate, the Gen-Probe assay was more sensitive than Ag-EIA; detection limits were respectively 2 X 10(3) c.f.u./ml (3.2 X 10(5) genomes) and 2.5 X 10(4) c.f.u./ml (4 X 10(6) genomes); detection levels 10-100 times less sensitive than culture. The two assays were also tested on nasopharyngeal aspirates or sputum specimens from 90 patients with respiratory infection; 67 of these were culture- or seronegative for M. pneumoniae and 23 were culture- or seropositive. Ag-EIA detected 21 (91%) of the latter but the Gen-Probe assay detected only 5 (22%). Both assays were negative with the 67 culture-/sero-negatives; there were no Gen-Probe assay positive/Ag-EIA negatives. Overall, it is concluded that although Ag-EIA and the Gen-Probe assay are effective substitutes for culture as a diagnostic procedure, there is a significant problem with samples which are culture-negative and from patients who have good serological evidence of current infection. Possible reasons for the disparity between the two assays are advanced.     

Human ovarian-carcinoma cell lines and companion xenografts: a disease-oriented approach to new platinum anticancer drug discovery

Summary A disease-oriented approach to the discovery of novel platinum anticancer drugs has been established through the setting up of parallel human ovarian-carcinoma cell lines and xenografts. The correlation between in vitro and in vivo antitumour activity was determined for four reference platinum agents (cisplatin, carboplatin, iproplatin and tetraplatin) in eight companion lines. Two methods of assessing antitumour effect were used in vitro (tritiated thymidine incorporation and sulforhodamine B staining) and three were applied in vivo [28-day treated/control (T/C) ratio, growth delay and specific growth delay]. In vitro, large differences in cytotoxicity across the cell lines were observed for each drug. This was also reflected in the xenografts for cisplatin and carboplatin and, to a lesser extent, for iproplatin. A correlation analysis of in vitro vs in vivo data revealed a high, statistically significant positive correlation for cisplatin and a strong positive correlation for carboplatin. However, for the two platinum(IV) drugs, the correlation was less good. In particular, tetraplatin was markedly less active in vivo (showing a general lack of activity against all of the tumour lines) than its in vitro potency against the cell lines predieted, resulting in poor correlation coefficients. These human tumour panels may be valuable for the elucidation of both cellular/molecular and corresponding in vivo pharmacological mechanisms of platinum drug resistance. Moreover, the HX/62 and SKOV-3 tumour lines, which exhibit a level of intrinsic resistance to the four reference agents both in vitro and in vivo (and which were derived from patients who had not received prior platinum therapy), represent particularly useful evaluation models for the discovery of novel broad-spectrum platinum drugs.This study was supported by grants to the Institute of Cancer Research from the Cancer Research Campaign and the Medical Research Council, the Johnson Matthey Technology Centre and Bristol Myers Squibb Oncology