Effect of Preload Alternations on a New Doppler Echocardiographic Index of Combined Systolic and Diastolic Performance

The objective of the study was to assess the effect of preload alternations on a nongeometric Doppler index of combined systolic and diastolic myocardial performance (MPI). Doppler echocardiography was performed during Valsalva maneuver, passive leg lifting, and after sublingual administration of nitroglycerin in 50 healthy volunteers (group 1) and 25 patients (group 2) with previous myocardial infarction. MPI was significantly lower in group 1 (0.34 +/- 0.04) compared with group 2 (0.52 +/- 0.14), P <.0005. In group 1 MPI was significantly increased during preload manipulations (P =. 001). The largest change in MPI was induced by nitroglycerin (0.034 +/- 0.05). In group 2 no significant changes in MPI were found. In both groups peak E-wave velocity (P <.0005), E/A-ratio (P <.0005), and E-wave deceleration time (P <.0005) were found to change during preload alternations. In conclusion, we found in normal subjects and to a lesser extent in patients with previous myocardial infarction that MPI is influenced by preload.     

Basophil histamine release, IgE, eosinophil counts, ECP, and EPX are related to the severity of symptoms in seasonal allergic rhinitis

BACKGROUND: Serum specific IgE, basophil histamine release, and blood eosinophil parameters are associated with allergic rhinitis, but investigations of the relationship to the severity of allergic symptoms are few and conflicting. Our study aimed to investigate the seasonal changes in the following laboratory tests: specific IgE, basophil histamine release, eosinophil counts, and serum and plasma eosinophil cationic protein (ECP) and eosinophil protein X (EPX), and to analyze, in detail, the relationship of each individual test to the severity of symptoms in rhinitis patients allergic to both birch and grass pollen. METHODS: The above tests were performed on blood samples obtained from 49 allergic rhinitis patients during the birch-pollen season, during the grass-pollen season, and after the seasons. Symptom-medication diaries were filled in during both pollen seasons. We used partial least square (PLS) analysis to establish an optimal statistical link between the symptom score and medication and the laboratory tests, in an investigator-independent way. RESULTS: Increases in specific IgE, basophil histamine release, eosinophil counts, serum ECP and EPX, and plasma EPX were observed from the birch-pollen season to the grass-pollen season, followed by a decrease from the grass-pollen season to after the pollen seasons, except for the specific IgE. No seasonal changes in plasma ECP and total IgE were seen. The PLS analysis found a relationship between symptom score and medication and the aggregate laboratory tests (F-test value 40.2, correlation 0.34 for the cumulative relation). However, the variation in laboratory tests could explain only half of the total variation in symptoms and less than a quarter of the total variation in medication. The symptom score and, to a minor degree, medication were especially correlated with the basophil histamine-release results, with a decreasing relevance of specific IgE, eosinophil counts, total IgE, serum and plasma EPX, and serum ECP. Plasma ECP was not related to the symptom score and medication. CONCLUSIONS: A significant relationship between the severity of allergic rhinitis and various allergic inflammatory markers was found but could account for only a minor part of the variation in the patients' evaluation of their disease.     

Microglial reactivity correlates to the density and the myelination of the anterogradely degenerating axons and terminals following perforant path denervation of the mouse fascia dentata.

Transection of the entorhino-dentate perforant path is a well known model for lesion-induced axonal sprouting and glial reactions in the rat. In this study, we have characterized the microglial reaction in the dentate molecular layer of the SJL/J and C57Bl/6 mouse. The morphological transformation of the microglial cells and their densitometrically measured Mac-1 immunoreactivity were correlated with the density of silver-impregnated axonal and terminal degeneration and the myelination of the degenerating medial and lateral perforant pathways. Anterograde axonal and terminal degeneration leads to: (i) altered myelin basic protein immunoreactivity with the appearance of discrete myelin deposits preferentially in the denervated medial and significantly less so in the lateral perforant path zone from day 2 after lesioning; (ii) an increase in number and Mac-1 immunoreactivity of morphologically-changed microglial cells in the denervated perforant path zones with more pronounced morphological transformation of microglia in the medial than in the lateral perforant path zones at day 2 but not day 5 after lesioning; and (iii) a linear correlation between the density of microglial Mac-1 reactivity and axonal degeneration in the medial but not in the lateral perforant path zone at two days postlesion, and a linear correlation in both zones at five days postlesion. We propose that the differentiated microglial response is due to the different densities of axonal and terminal degeneration, as observed in the individual cases. The finding of a potentiated or accelerated microglial activation in the medial as compared to the lateral perforant path zone suggests different kinetics of microglial activation in areas with degenerating myelinated and unmyelinated fibers.     

Diabetic intestinal growth adaptation and glucagon-like peptide 2 in the rat: effects of dietary fibre

BACKGROUND/AIMS: Dietary fibre influence growth and function of the upper gastrointestinal tract. This study investigates the importance of dietary fibre in intestinal growth in experimental diabetes, and correlates intestinal growth with plasma levels of the intestinotrophic factor, glucagon-like peptide 2 (GLP-2). METHODS: Male Wistar rats were randomised to the following groups: two streptozotocin-diabetic and two control groups fed either a fibre-containing or a fibre-free diet for three weeks. Intestinal weight, length, and morphometric data (villus height, villus area, crypt depth) were measured. Blood samples were obtained after two weeks for measurement of GLP-2 and enteroglucagon (glicentin, oxyntomodulin). RESULTS: The mean daily consumption of food in the two diabetic groups was 40% higher than in controls. In diabetic rats fed fibre, the increase in intestinal weight from day 0 to 20 was sixfold greater than that of the controls and small intestine weight per cm length was increased by 50%. In the diabetic rats fed a fibre-free diet, intestinal growth was 30% less than in diabetic rats fed fibre, and intestinal weight increased only threefold compared with controls. Morphometric data showed that the intestinal increase in diabetic rats fed fibre was due primarily to growth of the mucosal layer. Villus height and crypt depth increased 60% and 40% respectively, but by only 20% in fibre-free diabetic rats. The plasma levels of GLP-2 parallelled diabetic intestinal growth, whereas plasma levels of enteroglucagon increased regardless of the extent of intestinal growth. CONCLUSIONS: Intestinal growth in experimental diabetes is strongly influenced by the presence of dietary fibre. The effect may be mediated by GLP-2.     

The salvage of recurrent endometrial carcinoma in the vagina and pelvis

A retrospective analysis was performed on 93 patients who developed recurrent endometrial carcinoma in the pelvis, vaginal vault, and lower 1/3 vagina. There were 12 lower 1/3 vaginal recurrences, 24 vault recurrences and 57 pelvic recurrences from the 1005 patients treated between 1960 and 1976. Median time to recurrence was 30 months. Twenty-six patients had distant metastases also present at the time of recurrence in the sites mentioned above. Thirty-three percent of lower 1/3 vaginal recurrences, 12.5% of vault recurrences, and 5.3% of pelvic recurrences were salvaged with further treatment. The 10-year actuarial survival rates of isolated lower 1/3 vaginal, vaginal vault, and pelvic recurrences were 50%, 45%, and 24% respectively.     

Xenografts of mouse hippocampal tissue, exchange of laminar and neuropeptide specific nerve connections with the host rat brain

Immature hippocampal and fascia dentata tissue from embryonic and newborn C57 mice was grafted to the hippocampal region of newborn Kyoto rats. The age of the donor mice varied from embryonic day 13 to the day of birth, and the recipient rats from the day of birth up to 2 days. After survival times of from 5 weeks to 1 year the recipient brains were histologically processed for the tracing of host-xenograft connections by silver staining and electron microscopy of anterograde degeneration, AChE histochemistry, immunohistochemical demonstration of the neuropeptides CCK and enkephalin, and the histochemical Timm sulphide silver method, as well as stained by ordinary cell and fiber stains. The survival of the xenografts depended on the donor age, with less than 10% survival for newborn donors and 60-69% for E13-16 donors. The surviving xenografts developed an organotypic organization and retained a mouse-specific CCK-reactivity in the associational hilodentate system and the dentate mossy fibers. Judged by their positive AChE histochemistry most xenografts received a host rat cholinergic projection when placed in normal cholinoreceptive areas, including areas outside the normal reach of the septo-hippocampal system like the neocortex. Xenografts encroaching on the trajectory of the host rat commissural and perforant path projections or their terminal fields in fascia dentata received laminar and neuropeptide specific host projections. Electron microscopy of host rat perforant path fibers traced to the xenograft dentate molecular layer confirmed the laminar distribution and revealed numerous asymmetric synaptic contacts with spines. An efferent xenograft projection of CCK-reactive mouse mossy fibers into the host CA3 mossy fiber layer demonstrated that this cross-species, mouse to rat innervation also applied to the normal developmental rules, despite the, for the rat abnormal, CCK-content. The formation of laminar and neuropeptide specific mouse-rat nerve connections demonstrates the potentials of intracerebral neuronal grafting in basic and applied neurobiological research by providing new experimental models for the analysis of developmental and functional interactions between nerve cells.     

Red tattoos,ultraviolet radiation and skin cancer in mice

Ultraviolet radiation (UVR) induces skin cancer. The combination of UVR and red tattoos may be associated with increased risk of skin cancer due to potential carcinogens in tattoo inks. This combination has not been studied previously. Immunocompetent C3.Cg/TifBomTac hairless mice (n=99) were tattooed on their back with a popular red tattoo ink. This often used ink is banned for use on humans because of high content of the potential carcinogen 2‐anisidine. Half of the mice were irradiated with three standard erythema doses UVR thrice weekly. Time to induction of first, second and third squamous cell carcinoma (SCC) was measured. All UV‐irradiated mice developed SCCs. The time to the onset of the first and second tumor was identical in the red‐tattooed group compared with the control group (182 vs 186 days and 196 vs 203 days, P=ns). Statistically, the third tumor appeared slightly faster in the red‐tattooed group than in the controls (214 vs 224 days, P=.043). For the second and third tumor, the growth rate was faster in the red‐tattooed group compared with the control (31 vs 49 days, P=.009 and 30 vs 38 days, P=.036). In conclusion, no spontaneous cancers were observed in skin tattooed with a red ink containing 2‐anisidine. However, red tattoos exposed to UVR showed faster tumor onset regarding the third tumor, and faster growth rate of the second and third tumor indicating red ink acts as a cocarcinogen with UVR. The cocarcinogenic effect was weak and may not be clinically relevant.     

Are medical students being taught anatomy in a way that best prepares them to be a physician?

Reasoning in a clinical context is an attribute of medical expertise. Clinical reasoning in medical school can be encouraged by teaching basic science with a clinical emphasis. The aim of this study was to investigate whether anatomy is being taught in a way that facilitates the development of clinical reasoning. Two multiple‐choice tests on thoracic anatomy were developed using a modified Delphi approach with groups of four clinical consultants and four teachers, respectively, expressing their opinions about knowledge relevant to thoracic anatomy. Validity was assessed by administering the tests to clinical consultants, anatomy teachers, and pre‐course medical students. Post‐course medical students took both tests to explore the focus of the course, i.e., whether it facilitated clinical reasoning. The pre‐course students scored significantly lower than the teachers and post‐course students on both tests and lower than the consultants on the consultants’ test (P < 0.001 for all comparisons). The teachers significantly outperformed the consultants (P = 0.03 on the consultants’ test, P < 0.001 on the teachers’ test) and the medical students (P < 0.001 on both tests). The post‐course students scored significantly lower on the consultants’ test (P = 0.001) and significantly higher on the teachers’ test (P = 0.02) than the consultants. This study demonstrates poor performances by medical students on a test containing clinically relevant anatomy, implying that the teaching they have received has not encouraged clinical reasoning. Clin. Anat. 28:568–575, 2015. © 2015 Wiley Periodicals, Inc.