Depression prevalence in Type 2 diabetes is not related to diabetes-depression symptom overlap but is related to symptom dimensions within patient self-report measures: a meta-analysis.

AIM: Depression is common in Type 2 diabetes, yet rates vary. Overlap between symptoms of depression and diabetes may account for this variability in depression prevalence rates. We examined to what extent depression prevalence was a function of the proportion of depression-diabetes symptom overlap (items within symptom dimensions) and sample characteristics. METHODS: Electronic and hand searching of published and unpublished works identified 147 eligible papers. Of 3656 screened, 147 studies (149 samples, N = 17-229 047, mean sample age 25.4-82.8 years, with 152 prevalence estimates), using 24 validated depression questionnaires were selected. Sample size, publication type, sample type, gender, age, BMI, HbA1c , depression questionnaire and prevalence rates were extracted. RESULTS: Prevalence rates ranged from 1.8% to 88% (mean = 28.30%) and were higher in younger samples, samples with higher mean HbA1c and clinic samples. Diabetes-depression symptom overlap did not affect prevalence. A higher proportion of anhedonia, cognition, cognitive, negative affect and sleep disturbance symptoms, and a lower proportion of somatic symptoms were consistently associated with higher depression prevalence. CONCLUSIONS: The lack of an overall effect of diabetes-depression symptom overlap might suggest that assessment of depression in Type 2 diabetes is generally not confounded by co-occuring symptoms. However, questionnaires with proportionally more or fewer items measuring other symptom categories were associated with higher estimates of depression prevalence. Depression measures that focus on the cardinal symptoms of depression (e.g. negative affect and cognition), limiting symptoms associated with increasing diabetes symptomatology (e.g. sleep disturbance, cognitive) may most accurately diagnose depression.

Synthesis, topoisomerase I inhibitory activity, and in vivo evaluation of 11-azacamptothecin analogs.

A series of analogs based on a novel template, 11-aza-(20S)-camptothecin, were obtained from total synthesis and tested as potential anticancer drugs in the topoisomerase I enzyme cleavable complex assay. The parent compound 11-aza-(20S)-camptothecin (8) was derived from a Friedlander condensation between the known aminopyridine derivative 3-(3-amino-4-picolylidene)-p-toluidine and optically active tricyclic ketone 7. Compound 8 had activity approximately twice that of (20S)-camptothecin in the calf thymus topoisomerase I cleavable complex assay. Compounds were prepared wherein the 11-aza nitrogen atom was quaternized as either the corresponding N-oxide or methyl iodide. Compounds with quaternized N-11 showed improved water solubility and were equipotent to the clinically investigated camptothecin analog topotecan in the cleavable complex assay. These compounds were evaluated in vivo in nude mice bearing HT-29 human colon carcinoma xenografts. The analog 11-aza-(20S)-camptothecin 11-N-oxide was found to significantly retard tumor growth when compared to untreated controls. Finally, 7,10-disubstituted 11-azacamptothecin analogs were synthesized using Pd(0) coupling reactions of 10-bromo-7-alkyl-11-aza-(20S)-camptothecins 19 and 20, which in turn were available from a Friedlander condensation of the novel bromopyridine derivatives 17a and 17b with 7. Among the 10-substituted series, a number of analogs displayed extremely high in vitro potency against topoisomerase I and improved aqueous solubility. A significant number of the compounds were found to be active in whole cell cytotoxicity assays and several were evaluated in nude mice bearing the HT-29 tumor xenografts. The most effective of these proved to be (S)-11-aza-7-ethyl-10-(aminohydroximinomethyl)camptothecin trifluoracetic acid salt (27), a potent topoisomerase I inhibitor which demonstrated excellent efficacy in both short term and in extended in vivo assays. A comparison between in vitro enzyme data and in vivo data from nude mouse studies in other compounds in this series revealed a poor overall correlation between topoisomerase inhibition in vitro and antitumor efficacy in vivo.

Two general routes to 1,4-disubstituted-2,3,4,5-tetrahydro- 1H-3-benzazepines.

[structure] Two general routes to 1,4-disubstituted-2,3,4, 5-tetrahydro-1H-3-benzazepines are described. Both routes utilize an appropriately functionalized phenethylamino alcohol as the penultimate intermediate: the first route makes use of the reductive amination of a benzyl alkyl ketone with alpha-(aminomethyl)benzyl alcohol, while the second route utilizes the addition of a Grignard reagent to the oxazolidine derived from a substitued phenylacetaldehyde and alpha-(methylaminomethyl)benzyl alcohol. In all cases studied, the cis-1,4-disubstituted-2,3,4, 5-tetrahydro-1H-3-benzazepine was obtained as the major product.

Osteoid osteoma: the uniquely innervated bone tumor.

Osteoid osteomas are benign bone-forming tumors that despite their small size (<2.0 cm) characteristically produce severe nocturnal bone pain that is relieved by aspirin. This typical clinical presentation is virtually unique among bone tumors. Histologically, osteoid osteomas are circumscribed nodules of woven bone and osteoid with prominent osteoblastic rimming (the nidus), surrounded by thickened cortical and trabecular bone and loose fibrovascular tissue (the reactive zone). Prostaglandins mediate the pain of osteoid osteomas, but there have been few studies of their innervation. We investigated 34 osteoid osteomas using a streptavidin immunohistochemical technique and a panel of antibodies to neural and neural-associated antigens (phosphorylated neurofilament, neurofilament, and S-100 protein). Whenever possible, sections of the nidus and the reactive zone were stained. As controls, we stained other bone tumors that can be painful, including 10 osteoblastomas, 5 osteosarcomas, 6 giant cell tumors, 4 chondroblastomas, 3 aneurysmal bone cysts, and 6 cases of fibrous dysplasia. Twenty-five osteoid osteomas contained phosphorylated neurofilament-, neurofilament-, and/or S-100-positive nerve fibers in the reactive zone around the nidus and/or in the nidus. The nerve fibers were larger and more abundant in the reactive zone than in the nidus, and they were occasionally visible on hematoxylin- and eosin-stained slides on retrospective review. The smaller nerve fibers within the nidi were never identified, even after extensive review of those slides. In the nine cases in which nerve fibers were not identified, the sampled tissue consisted only of nidus. None of the control "bone tumors" contained detectable nerve fibers within their substance or in the adjacent peripheral bone. The nerve supply of osteoid osteoma seems unique among bone tumors, and it might serve as a marker in diagnostically difficult cases.