A prearranged mentorship program: can it work long distance?

The results of a series of scanning electron microscopical studies were used to construct a model for the vascular pathways in the inner ear. Corrosion cast preparations of the vessels of the inner ear of the adult rat were used in this study. The inner ear is, like a hand, an end organ containing four sense organs (cochlea, saccule, utricle and the cristae ampullaris). All these specific inner ear structures have their own vascular supply. We have developed a blood flow diagram of the inner ear. This model was used for a classification of different types of ischemia in the inner ear and forms a concept for some forms of sensorineural hearing loss and vertigo. Four types of inner ear ischemia are proposed. In type I (a or b) of inner ear ischemia only the vessels of the cochlea are involved resulting in two types of hearing loss without vertigo. Type II is characterized by ischemia of a part of the cochlea and a part of the vestibular system. In type III (a or b) only the vestibular system is involved, while in type IV no blood circulation will be present in the inner ear resulting in total deafness and severe vertigo. Inner ear partition at ultramicroscopical level of these structures may be possible in the future and new imaging techniques will probably support the vascular schematic model presented in this study.     

Subchronic dietary toxicity of strychnine: bobwhite quail are less sensitive than mallard ducks

PURPOSE: This study was undertaken to evaluate in vivo the effect of recombinant hirudin (r-hirudin [HBW 023]), a potent thrombin inhibitor, on the process of microvascular thrombus formation and recanalization. METHODS: Thrombosis was induced photochemically in distinct arterioles (n = 25) and venules (n = 30) of the ear of 16 hairless hr/hr mice (8 to 10 weeks old, 25 to 30 g of body weight). r-Hirudin (1 mg/kg of body weight) was administered intravenously directly before thrombus induction; saline-treated animals served as controls. Thrombus formation (i.e., first platelet deposition at the endothelial lining [FPD]; inner luminal diameter reduction to 50% [D/2]; complete vessel occlusion [CVO]), vessel recanalization, microcirculatory parameters, and leukocyte-endothelial cell interaction were analyzed by means of intravital fluorescence microscopy. RESULTS: Hirudin significantly delayed the process of thrombus formation compared with saline-treated controls in both arterioles (FPD: 381 +/- 80 vs 137 +/- 25 seconds, P < 0.05; D/2: 627 +/- 49 vs 501 +/- 71 seconds; CVO: 925 +/- 78 vs 854 +/- 60 seconds) and venules (FPD: 173 +/- 11 vs 59 +/- 4 seconds; D/2: 342 +/- 54 vs 228 +/- 27 seconds; CVO: 541 +/- 85 vs 344 +/- 43 seconds; P < 0.05). In addition, r-hirudin-treated animals showed an increased rate of vessel recanalization at 24 hours after thrombus induction (arterioles: 54% [7 of 13] vs 0% [0 of 12], P < 0.05; venules: 77% [10 of 13] vs 53% [9 of 17]), whereas microcirculatory parameters and leukocyte-endothelial cell interaction were not affected. CONCLUSION: Our data indicate that r-hirudin not only counteracts the process of thrombus formation but also promotes vessel recanalization, thus supporting its use in clinical microvascular surgery.     

A novel bipartite splicing enhancer modulates the differential processing of the human fibronectin EDA exon

EDA is a facultative type III homology of human fibronectin encoded by an alternative spliced exon. The EDA+ and EDA- mRNA forms show a cell type specific distribution with their relative proportion varying during development, aging and oncogenic transformation. We have previously demonstrated that an 81 bp nucleotide sequence within the exon itself is essential for differential RNA processing. Fine mapping of cis acting elements within this region has been carried out to identify possible target sites for the modulation of alternative splicing. There are at least two short nucleotide sequences involved. Element A (GAAGAAGA) is a positive modulator for the recognition of the exon, its deletion results in constitutive exclusion of the EDA exon. Element B (CAAGG) is a negative modulator for exon recognition, its deletion results in constitutive inclusion of the EDA exon. This bipartite structure of the splicing enhancer is a novel feature of the mammalian exons.     

Mammographic findings after stereotaxic biopsy of the breast performed with large-core needles

Colorectal cancer generally affects men and women in the later decades of life. Typically patients present with bowel obstruction and/or chronic anemia. The epidemiology, presentation, and prognosis of cecal carcinoma, the third most common colorectal cancer, is similar to other cancers of the large bowel. Cecal and other colorectal cancers rarely present in adolescence. In this case report, we describe a 19-year-old woman presenting with a pelvic mass and elevated tumor markers with the presumed diagnosis of ovarian cancer, who was found to have cecal carcinoma at laparotomy. This case illustrates that colorectal cancer, although rare, should be considered in the differential diagnosis of a pelvic mass in young women who present with anemia, constitutional symptoms, and elevated tumor markers.     

Comparison of tamoxifen effects on the actions of triiodothyronine or growth hormone in the ovariectomized-hypothyroid rat

Recent studies have suggested that a subset of estrogen responses arise via modulation of triiodothyronine (T3) actions, and depend on T3 for expression: other estrogen responses are not T3-dependent. Moreover, tamoxifen acts as a full estrogen agonist in T3-dependent responses but behaves as an antiestrogen in T3-independent responses. T3 directly induces a variety of metabolic enzymes and proteins, and also induces rat growth hormone (GH). Thus, some T3-dependent tamoxifen effects might reflect modulation of GH rather than T3 actions. To address this issue, tamoxifen effects on somatotropic and metabolic actions of T3 and GH were compared in ovariectomized rats with methimazole-induced hypothyroidism. Rats were given T3 (10 micrograms/kg/day) or ovine GH (2 mg/kg/day) with or without tamoxifen (0.5 mg/kg/day) for 30 days. GH was poorly effective in producing a sustained increase in somatic growth in hypothyroid rats compared to T3; nonetheless, GH effects to increase body weight, tibia length and serum insulin-like growth factor I while decreasing fat mass and evoking small increases in body temperature were not inhibited by tamoxifen. Tamoxifen also did not inhibit GH trends to increase tibia bone mineral density. T3 increased body temperature, insulin-like growth factor I levels and all measures of somatic growth and, unlike GH, increased food intake and tended to decrease tibia bone mineral density. Tamoxifen inhibited the somatotropic actions of T3 (including increases in insulin-like growth factor I levels), and produced significant increases in tibia bone mineral density only in T3-treated rats. Tamoxifen had no effect on T3 actions to increase food intake or body temperature. T3 alone increased fat mass and exhibited a tendency to decrease serum triglycerides: tamoxifen had no effect on these parameters in the absence of T3. However, coadministration of tamoxifen with T3 produced a marked decrease in fat mass and increased serum triglycerides. GH had no effect on serum triglycerides in either the presence or absence of tamoxifen. Serum glucose levels appeared normal in all groups. The data indicate that multiple tamoxifen effects on growth and metabolism may reflect modulation of T3 rather than GH actions.     

The hippocampus: normal anatomy and pathology

The hippocampus is a complex and fascinating region of the brain that has enormous clinical significance. Specifically, small imaging abnormalities may cause major symptoms. We believe that the detection of these lesions will be improved if imaging clinicians have an organized reference that facilitates identification of the cellular zones that comprise the hippocampus.     

Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P

We evaluated the effects of nitric oxide (NO) generators and endogenous production of NO elicited by substance P (SP) in the angiogenesis process. Angiogenesis was monitored in the rabbit cornea in vivo and in vitro by measuring the growth and migration of endothelial cells isolated from coronary postcapillary venules. The angiogenesis promoted in the rabbit cornea by [Sar9]-SP-sulfone, a stable and selective agonist for the tachykinin NK1 receptor, and by prostaglandin E1 (PGE1), was potentiated by sodium nitroprusside (SNP). Conversely, the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), given systemically, inhibited angiogenesis elicited by [Sar9]-SP-sulfone and by PGE1. Endothelial cells exposed to SNP exhibited an increase in thymidine incorporation and in total cell number. Exposure of the cells to NO generating drugs, such as SNP, isosorbide dinitrate, and glyceryl trinitrate, produced a dose-dependent increase in endothelial cell migration. Capillary endothelial cell proliferation and migration produced by SP were abolished by pretreatment with the NO synthase inhibitors N omega-mono-methyl-L-arginine (L-NMMA), N omega-nitro-L-arginine (L-NNA), and L-NAME. Exposure of the cells to SP activated the calcium-dependent NO synthase. Angiogenesis and endothelial cell growth and migration induced by basic fibroblast growth factor were not affected by NO synthase inhibitors. These data indicate that NO production induced by vasoactive agents, such as SP, functions as an autocrine regulator of the microvascular events necessary for neovascularization and mediates angiogenesis.