Sarcoid-like lymphadenopathy mimicking metastatic testicular cancer

A case of nonseminomatous testicular cancer and enlarged mediastinal lymph nodes, which were interpreted as metastases, is reported. When there was no change after two courses of chemotherapy, a mediastinoscopy was performed and the results showed sarcoidosis.     

Cloning and expression analysis of the chick DAN gene, an antagonist of the BMP family of growth factors.

Differential screening-selected gene aberrative in neuroblastoma (DAN) is a member of a cystine knot protein family that includes Cerberus and Gremlin. First isolated in a screen to identify genes down-regulated in transformed rat fibroblasts, DAN has subsequently been cloned in Xenopus, mouse, and human. Overexpression of DAN suppresses the transformed phenotype and retards the cell's entry into S phase. Biochemical analyses have demonstrated DAN's ability to bind bone morphogenetic proteins and antagonize their signaling activity. In this study, chick DAN was cloned and sequenced, revealing a conserved cystine knot region as well as an N-glycosylation site. A riboprobe was designed from the 3' chick DAN coding sequence and used for analysis of DAN in the developing chick embryo by in situ hybridization. Chick DAN was expressed beginning at stage 10 in the developing somites and the medial otic epithelium. Expression in the neural layer of the eye became apparent at stage 14. By stage 17, expression had expanded to the base of the hindbrain. Limb bud labeling began at stage 20, whereas expression in the branchial arches appeared at stage 25. Chick DAN expression generally corresponded to that of mouse DAN expression as shown by comparative in situ hybridization. However, chick DAN was found in the otic epithelium and notochord, whereas mouse DAN was restricted to the overlying otic ectomesenchyme and was absent from the notochord. This observation suggests that DAN may play different roles in chick and mouse otic and notochord development.     

Problems with a ‘target’ approach to access in primary care: a qualitative study

We report an analysis of the qualitative phase of a study of patients' and carers' views of primary care services, focusing on their experiences of access to face-to-face general practitioner (GP) consultations during the period when new access policies were being implemented. Practices interpreted the new policy in various ways; restricted interpretations, including restriction of access to telephone booking, could cause distress to patients. Patients and carers welcomed flexible interpretations of the policy that offered choice, such as a choice of GP, or of booking in advance.     

A second look at second-order belief attribution in autism

Compared the performance of autistic and mentally retarded subjects, all of whom had passed a standard first-order test of false belief, on a new second-order belief task 12 autistic and 12 mentally retarded subjects, matched on verbal mental age (assessed by PPVT and a sentence comprehension subtest of the CELF) and full-scale IQ were given two trials of a second-order reasoning task which was significantly shorter and less complex than the standard task used in all previous research. The majority of subjects in both groups passed the new task, and were able to give appropriate justifications to their responses. No group differences were found in performance on the control or test questions. Findings are interpreted as evidence for the role of information processing factors rather than conceptual factors in performance on higher order theory of mind tasks.This study was supported by a grant from the National Institute of Deafness and Other Communication Disorders (1RO1 DC 01234). We thank Jason Barker for his extensive help with this study. We are also very grateful to the schools where the study was conducted including the League School, and the public school systems in the following towns in Massachusetts: Hanover, Hanson, Hingham, Milton, Plymouth, and Rockland. We offer special thanks to Alan Dewey, Mary Dollar, Sandy D'Giacomo, Herman Fishbein, William Griffin, Nancy Kearns, Judy Monahan, Debbie Newhall, Cay Riley, Robert Sherman, and Kathy Staska for their continued support of our research.     

Evaluation of the E test for the assessment of synergy of antibiotic combinations against multiresistant Pseudomonas aeruginosa isolates from cystic fibrosis patients

The determination of synergistic effects of antimicrobial drug combinations can lead to improved therapeutic options in the antibiotic treatment of cystic fibrosis patients who are chronically infected with multiresistant Pseudomonas aeruginosa isolates. The aim of this study was to evaluate the performance of the E test versus the standard agar dilution checkerboard susceptibility test in the assessment of synergy and, in addition, to determine the activity of two antimicrobial combinations against 163 multiresistant P. aeruginosa isolates from cystic fibrosis patients. The agreement between the checkerboard method and the E test was excellent (>90%) for nonmucoid as well as mucoid isolates from cystic fibrosis patients. The rate of synergy was higher for the antibiotic combination of ceftazidime and tobramycin (28.8% of the cystic fibrosis strains) than for the combination of meropenem and tobramycin (19.0%). However, the probability of synergy for the second antibiotic combination increased significantly when the synergy of the first antibiotic combination had already been demonstrated (Fischer’s exact test, p=0.049). The results show that the E test is a valuable and practical method for routine microbiological diagnostics and can aid in the selection of improved antibiotic options in the treatment of cystic fibrosis patients chronically infected with P. aeruginosa.     

Growth inhibition of estrogen independent MXT mouse mammary carcinomas in mice treated with an agonist or antagonist of LH-RH,an analog of somatostatin,or a combination

Summary Female BDF₁ mice inoculated with MXT (3.2) estrogen independent mouse mammary carcinoma were treated for three weeks with microcapsules of the luteinizing hormone-releasing hormone (LH-RH) agonist [D-Trp⁶]LH-RH, the antagonist SB-75, the somatostatin analog RC-160, or combinations. The lack of estrogen dependence of the tumor was proved by bilateral surgical ovariectomy, which had no effect. In two experiments, treatment with 25µg/day doses of each analog alone resulted in a significant inhibition of tumor growth as shown by a 40–53% inhibition of tumor volumes, 38–43% decrease in tumor weights, and histological signs of tumor regression. However, the combination of SB-75 or [D-Trp⁶]LH-RH with somatostatin analog RC-160 caused greater reduction of tumor volume (68 and 61%) or tumor weights (59 and 56%), than single analogs, and histologically the occurrence of apoptosis and decrease in AgNOR numbers was more pronounced in the groups receiving combination therapy. Specific binding sites for [D-Trp⁶]LH-RH, EGF, and IGF-I were demonstrated in the tumor membranes. The binding capacity of LH-RH receptors was decreased by treatment with the analogs, the greatest down-regulation being caused by combination therapy. A significant decrease in EGF binding capacity was observed after treatment with the LH-RH analogs, alone or especially in combination with somatostatin analog RC-160. The combination of these analogs also caused a reduction in IGF-I receptors. The finding that LH-RH agonists and antagonists and somatostatin analogs inhibit the growth of estrogen independent mammary tumors, and that combinations are more effective than single analogs, might be of practical importance in human breast cancer therapy.