18F-FDG PET/CT for detecting nodal metastases in patients with oral cancer staged N0 by clinical examination and CT/MRI.

(18)F-FDG PET has a high accuracy in staging head and neck cancer, but its role in patients with clinically and radiographically negative necks (N0) is less clear. In particular, the value of combined PET/CT has not been determined in this group of patients. METHODS: In a prospective study, 31 patients with oral cancer and no evidence of lymph node metastases by clinical examination or CT/MRI underwent (18)F-FDG PET/CT before elective neck dissection. PET/CT findings were recorded by neck side (left or right) and lymph node level. PET/CT findings were compared with histopathology of dissected nodes, which was the standard of reference. RESULTS: Elective neck dissections (26 unilateral, 5 bilateral; a total of 36 neck sides), involving 142 nodal levels, were performed. Only 13 of 765 dissected lymph nodes harbored metastases. Histopathology revealed nodal metastases in 9 of 36 neck sides and 9 of 142 nodal levels. PET was TP in 6 nodal levels (6 neck sides), false-negative in 3 levels (3 neck sides), true-negative in 127 levels (23 neck sides), and false-positive in 6 levels (4 neck sides). The 3 false-negative findings occurred in metastases smaller than 3 mm or because of inability to distinguish between primary tumor and adjacent metastasis. TP and false-positive nodes exhibited similar standardized uptakes (4.8 +/- 1.1 vs. 4.2 +/- 1.0; P = not significant). Sensitivity and specificity were 67% and 85% on the basis of neck sides and 67% and 95% on the basis of number of nodal levels, respectively. If a decision regarding the need for neck dissection had been based solely on PET/CT, 3 false-negative necks would have been undertreated, and 4 false-positive necks would have been overtreated. CONCLUSION: (18)F-FDG PET/CT can identify lymph node metastases in a segment of patients with oral cancer and N0 neck. A negative test can exclude metastatic deposits with high specificity. Despite reasonably high overall accuracy, however, the clinical application of PET/CT in the N0 neck may be limited by the combination of limited sensitivity for small metastatic deposits and a relatively high number of false-positive findings. The surgical management of the N0 neck should therefore not be based on PET/CT findings alone.     

Transgenic mice expressing constitutive active MAPKAPK5 display gender-dependent differences in exploration and activity

Background  

The mitogen-activated protein kinases, MAPKs for short, constitute cascades of signalling pathways involved in the regulation of several cellular processes that include cell proliferation, differentiation and motility. They also intervene in neurological processes like fear conditioning and memory. Since little remains known about the MAPK-Activated Protein Kinase, MAPKAPK5, we constructed the first MAPKAPK knockin mouse model, using a constitutive active variant of MAPKAPK5 and analyzed the resulting mice for changes in anxiety-related behaviour.     

Plasmodium vivax and P. chabaudi: inter-species cross-reacting antigens

A monoclonal antibody raised by immunization of BALB/c mice with erythrocytic stages of Plasmodium vivax was shown to react with asexual erythrocytic stages of P. chabaudi. The cross-reactivity molecules are antigens of 200 and 148 kDa in P. vivax and of 190 and 70 kDa in P. chabaudi. Immunofluorescence studies of the erythrocytic stages of P. vivax and P. chabaudi indicated that expression of these antigens increased as the parasites' developed from the ring stage to the schizont stage. In the mature trophozoites of P. chabaudi, immunoelectron microscopy revealed clusters of antigen distributed in the cytoplasm of the parasitized erythrocyte. In the schizont, packets of antigen were found associated with the parasitophorous vacuole and the cytoplasm of the infected host cell. Received: 19 March 1996 / Accepted: 28 August 1996     

Computer-assisted diagnosis of rheumatic disorders.

A review of the literature regarding computer-assisted diagnosis of rheumatic diseases is presented. After a general outline of the history and goals of computer programs intended to support physicians in the diagnostic process, 14 systems or projects are described. The scope of seven of these is general internal medicine, and the other seven are intended exclusively for rheumatic problems. The majority of these systems are prototypes. To date, none of them is widely used by physicians. Preliminary evaluation studies and/or independent reviews have been reported for all of the systems. The need for further evaluation studies is recognized, and strategies to carry these out are outlined. Furthermore, the potential usefulness for patient care and education is discussed. It is concluded that a new and interesting field is being developed that deserves more attention among rheumatologists.     

Familias Unidas: The Efficacy of an Intervention to Promote Parental Investment in Hispanic Immigrant Families

This paper reports a test of the efficacy of Familias Unidas, a Hispanic-specific, ecologically focused, parent-centered preventive intervention, in promoting protection against and reducing risk for adolescent behavior problems. Specifically, the intervention was designed to foster parental investment, reduce adolescent behavior problems, and promote adolescent school bonding/academic achievement, all protective factors against drug abuse and delinquency. One-hundred sixty seven Hispanic families of 6th and 7th grade students from three South Florida public schools were stratified by grade within school and randomly assigned to intervention and no-intervention control conditions. Results indicated that Familias Unidas was efficacious in increasing parental investment and decreasing adolescent behavior problems, but that it did not significantly impact adolescent school bonding/academic achievement. Summer-vacation rates of adolescent behavior problems were six times higher in the control condition than in the intervention condition. Furthermore, change in parental investment during the intervention was predictive of subsequent levels of adolescent behavior problems. The findings suggest that Familias Unidas is efficacious in promoting protection and reducing risk for adolescent problem behaviors in poor immigrant Hispanic families.     

In-vivo carcinogenicity of 2-nitro-oxaphenalenes

2-Nitro-oxaphenalenes are synthetic chemicals which were synthesized in the authors' laboratory. They are the most efficient mutagenic compounds on mammalian cells in culture. They are chemically related to the nitro-naphthofuran family by the displacement of the heterocycle on the naphthalene ring. Since nitro-naphthofurans have a strong mutagenic activity in bacterial tests without metabolic activation and are active in-vivo carcinogens, the purpose of this study was to demonstrate the carcinogenic activity of two 2-nitro-oxaphenalenes. The two compounds were injected s.c. into Wistar rats initially 6-weeks-old. They were dissolved in dimethylsulfoxide (DMSO) at a concentration of 1 mg/ml. A s.c. injection of 0.5 ml containing 0.5 mg of carcinogen was given once a week in the neck of each animal tested. Five control animals were not injected and five animals received 0.5-ml injection of DMSO every week to serve as a control. The animals developed tumors only at the site of injection. The tumors were classified as high grade fibrosarcomas. This experiment demonstrates that: (i) 2-nitro-oxaphenalenes are very active in-vivo carcinogens in rats; (ii) there is a good correlation between the high mutagenic activity especially in mammalian tests and the strong carcinogenicity of the compounds; and (iii) the presence of a 6-methoxy group increases by two-fold the carcinogenic potential.     

Are hypodense eosinophils in children activated or immature?

In patients with allergic asthma and rhinitis high numbers of hypodense eosinophils (HE) have been demonstrated. In a previous study we reported that asthmatic and healthy children had more HE than their adult counterparts. We assumed that this might, in part, he due to the presence of immature eosinophils in children. To distinguish between immature and activated eosinophils, determination of eosinophil cationic protein (ECP) might be interesting as it is known that high serum levels of ECP are associated with increased activation of eosinophiis. In this study we determined (he levels of ECP in scrum in asthmatic and healthy children and adults trying to distinguish activated from immature eosinophils. We found that ECP levels were not increased in children (healthy and asthmatic) compared to adults (healthy and asthmatic). This supports the hypothesis that increased numbers of HE in childhood are, at least in part, immature eosinophils. Nevertheless, we could confirm that inflammation was present in children because soluble interleukin-2-receptor (slL-2R), a marker of lymphocyte activation, was higher in asthmatic children as compared to healthy children. IL-6, a marker of macrophage/monocyte activation, was not different in the different patient groups. We conclude that although signs of inflammation are present in childhood asthma, the increased numbers of HE in children are in part due to the presence of immature eosinophils.     

Stereospecific monoclonal antibodies to nicotine and cotinine and their use in enzyme-linked immunosorbent assays

Stereospecific monoclonal antibodies (McAb) have been prepared against the tobacco alkaloid (S)-(-)-nicotine and its major metabolite (S)-(-)-cotinine. Nine anti-nicotine and 4 anti-cotinine hybridomas, selected by a screening procedure that utilized immunoprecipitation of the ³H-labeled natural isomers of nicotine or cotinine, were grown in the ascites fluid of pristane-primed syngeneic BALB/c mice. Antibodies in concentrations up to 7.5 mg/ml ascites and with binding affinities that generally exceeded 10⁸ M⁻¹ were obtained. Enzyme-linked immunosorbent assays (ELISAs) were developed in which nicotine or cotinine derivatives bound covalently to poly- -lysine werecoated onto wells of polyvinyl chloride microtiter plates. Coated wells were incubated sequentially with McAb in the presence or absence of inhibitor, rabbit anti-mouse immunoglobulin, then horseradish peroxidase-labeled protein A (HRP-SpA) before addition of substrate. The antibodies are highly specific and show minimal cross-reactivity with several nicotine metabolites and other structurally related compounds. In the respective assays, only 0.25 ng (S)-(-)-nicotine and 0.12 ng (S)-(-)-cotinine are required to give 50% inhibition of antibody binding, and as little as 0.05 ng nicotine and 0.02 ng cotinine give 15% inhibition. These assays are 5–10 times more sensitive than analogous ELISAs developed with rabbit antisera and HRP-SpA or conventional radioimmunoassays (RIAs) that utilize the rabbit antisera and ³H-labeled ligands. There was good correlation between the levels of nicotine (r = 0.967) found in saliva samples from smokers and non-smokers assayed by McAb-based ELISAs and conventional RIAs.     

Patient and carer satisfaction with ''hospital at home'': quantitative and qualitative results from a randomised controlled trial.

BACKGROUND: 'Hospital At Home' schemes are set to increase in the United Kingdom (UK) in response to the NHS Plan. To date, little detailed work has been done on the acceptability of these schemes to patients and their carers. AIM: To compare Hospital at Home patient and carer satisfaction with hospital care. DESIGN OF STUDY: Pragmatic randomised controlled trial. SETTING: Consecutive patients assessed as suitablefor the Leicester Hospital at Home scheme were randomised to Hospital at Home or one of three acute hospitals in the city. METHOD: Patient satisfaction was assessed two weeks after randomisation, or at discharge if later using a six-item questionnaire. Patients' and carers' views of the services were assessed by semistructured interviews. RESULTS: One hundred and two patients were randomised to Hospital at Home and 97 to hospital. Forty-eight (47%) patients in the Hospital at Home arm and 35 (36%) in the hospital arm completed the satisfaction questionnaire, representing 96% and 85% of those eligible, respectively. Total scores were significantly higher in the Hospital at Home (median = 15) than in the hospital group (median = 12). (P<0.001, Mann-Whitney U-test.) Responses to all six questions favoured Hospital at Home, with all but one of these differences being statistically significant. In the Hospital at Homegroup, 24 patients and 18 of their carers were interviewed; in the hospital group 18 patients and seven of their carers were interviewed. Themes emerging from these interviews were that patients appreciated the more personal care and better communication offered by Hospital at Home and placed great value on staying at home, which was seen to be therapeutic. Patients largely felt safe in Hospital at Home, although some would have felt safer in hospital. Some patients and carers felt that better medical care would have been provided in hospital. Carers felt that the workload imposed by Hospital at Home was no greater than by hospital admission and that the relief from care duties at home would be counterbalanced by the added strain of hospital visiting. CONCLUSIONS: Patient satisfaction was greater with Hospital at Home than with hospital. Reasons included a more personal style of care and a feeling that staying at home was therapeutic. Carers did not feel that Hospital at Home imposed an extra workload.