Pharmacological therapy of vascular malformations of the gastrointestinal tract.

Vascular malformation (AVM) in the gastrointestinal tract is an uncommon, but not rare, cause of bleeding and iron deficiency anemia, especially in an aging population. While endoscopic coagulative therapy is the method of choice for controlling bleeding, a substantial number of cases require additional therapy. Adjunctive or even primary phamacotherapy may be indicated in recurrent bleeding. However, there is little evidence-based proof of efficacy for any agent. The bulk of support is derived from anecdotal reports or case series. The present review compares the outcome of AVM after no intervention, coagulative therapy or focus on pharmacological agents. Most of the literature encompasses two common AVMs, angiodysplasia and hereditary hemorrhagic telangiectasia. Similarly, the bulk of information evaluates two therapies, hormones (estrogen and progesterone) and the somatostatin analogue octreotide. Of these, the former is the only therapy evaluated in randomized trials, and the results are conflicting without clear guidelines. The latter therapy has been reported only as case reports and case series without prospective trials. In addition, other anecdotally used medications are discussed.     

Benefits of combined balloon pumping and percutaneous cardiopulmonary bypass.

Sixteen patients (2 women, 14 men) aged 29 to 72 years with continued cardiogenic shock during intraaortic balloon pumping (IABP) had additional treatment with percutaneous cardiopulmonary bypass (PBY). Cause of cardiogenic shock was myocardial infarction in 7 (3 survived), failed percutaneous transluminal coronary angioplasty requiring emergency coronary artery bypass grafting in 5, postoperative aortic valve replacement in 1, postoperative emergency coronary artery bypass grafting in 1, after cardiac transplantation in 1, and bridging to transplantation in 1. Mean blood pressure with PBY and IABP combined was 75 mm Hg versus 60 mm Hg with IABP off. Percutaneous cardiopulmonary bypass flows ranged from 0.8 to 2.1 L/min with a mean flow of 1.3 L/min. Time on IABP ranged from 24 hours to 1 week. Time on IABP to PBY ranged from 1 to 20 hours, and time on PBY ranged from 65 minutes to 20 hours. Ten of 16 (63%) were successfully weaned, and 3 died after weaning. Seven of 16 (44%) survive. Combined IABP with PBY appears to be a better therapy than either one individually. Staging the therapy as the balloon first in and last out appears to be a good methodology.     

Expression of keratin K2e in cutaneous and oral lesions: association with keratinocyte activation,proliferation, and keratinization

The cytoskeleton in keratinocytes is a complex of highly homologous structural proteins derived from two families of type I and type II polypeptides. Keratin K2e is a type II polypeptide that is expressed in epidermis late in differentiation. Here we report the influence of keratinocyte activation, proliferation, and keratinization on K2e expression in samples of cutaneous and oral lesions. The normal expression of K2e in the upper spinous and granular layers of interfollicular epidermis is increased in keloid scars but showed distinct down-regulation in psoriasis and hypertrophic scars where keratinocytes are known to undergo activation. Unlike normal and psoriatic skin, K2e expression in hypertrophic and keloid scars began in the deepest suprabasal layer. In cutaneous basal and squamous cell carcinomas, K2e was absent in most tumor islands but the overlying epidermis showed strong expression. No significant K2e expression in nonkeratinized or keratinized oral epithelia, including buccal mucosa, lateral border of tongue and gingiva was detected. In oral lichen planus K2e expression was undetectable, but in benign keratoses of lingual mucosa induction of K2e along with K1 and K10 was observed. In mild-to-moderate oral dysplasia with orthokeratinization, K2e was highly expressed compared with parakeratinized areas but in severe dysplasia as well as in oral squamous cell carcinoma, K2e expression was undetectable. Taken together, the data suggest that K2e expression in skin is sensitive to keratinocyte activation but its up-regulation in oral lesions is a reflection of the degree of orthokeratinization.     

Recombinant tumor necrosis factor alpha does not inhibit the growth of African trypanosomes in axenic cultures

Mice whose tumor necrosis factor alpha (TNF-alpha) genes were disrupted developed higher levels of parasitemia than wild-type mice following infection with Trypanosoma congolense IL1180 or T. brucei brucei GUTat3.1, confirming the results of earlier studies. To determine whether TNF-alpha directly affects the growth of these and other bloodstream forms of African trypanosomes, we studied the effects of recombinant mouse, human, and bovine TNF-alpha on the growth of two isolates of T. congolense, IL1180 and IL3338, and two isolates of T. brucei brucei, GUTat3.1 and ILTat1.1, under axenic culture conditions. The preparations of recombinant TNF-alpha used were biologically active as determined by their capacity to kill L929 cells. Of five recombinant TNF-alpha lots tested, one lot of mouse TNF-alpha inhibited the growth of both isolates of T. brucei brucei and one lot of bovine TNF-alpha inhibited the growth of T. brucei brucei ILTat1.1 but only at very high concentrations and without causing detectable killing of the parasites. The other lots of mouse recombinant TNF-alpha, as well as human TNF-alpha, did not affect the growth of any of the test trypanosomes even at maximal concentrations that could be attained in the culture systems (3,000 to 15,000 U of TNF-alpha/ml of medium). These results suggest that exogenously added recombinant TNF-alpha generally does not inhibit the growth of African trypanosomes under the culture conditions we used. The impact of TNF-alpha on trypanosome parasitemia may be indirect, at least with respect to the four strains of trypanosomes reported here.     

Progressive amplification and overexpression of the eukaryotic initiation factor 4E gene in different zones of head and neck cancers.

PURPOSE: Eukaryotic initiation factor 4E (eIF4E) binds to mRNA as the initial rate-limiting step in protein synthesis. Amplification and overexpression of the eIF4E gene has been associated with malignant transformation. The objectives of this study were to 1) quantify the eIF4E gene in head and neck squamous cell carcinoma (HNSCC) specimens, 2) quantify eIF4E protein elevation and examine its association with eIF4E gene amplification, and 3) determine whether there is progression in eIF4E gene amplification and protein overexpression in the tumor-free resection margin, the transition zone, and the tumor core of HNSCC specimens. MATERIALS AND METHODS: Eighteen HNSCC specimens were divided into three zones: 1) tumor core; 2) transition zone; and 3) "tumor-free" margin. Competitive polymerase chain reaction was performed to determine eIF4E gene copy number. eIF4E protein expression was quantified using Western blot analysis. RESULTS: All 18 HNSCC specimens tested had significant eIF4E gene amplification (4.3+/-1.2; P < .05). In contrast, none of the 10 benign specimens from noncancer patients had any eIF4E gene amplification (1.1+/-0.5). In the 12 HNSCC specimens examined for the three zones, the tumor core and transition zone showed eIF4E gene amplification (5.2+/-1.1 and 3.5+/-0.9, respectively) compared with the "tumor-free" margin (2.1+/-1.1; P < .05). The tumor core and transition zone showed significant efF4E protein elevation (15.5+/-9.3, 4.4+/-4.6, respectively) compared with the "tumor-free" margin (0.9+/-0.5, P < .05). CONCLUSIONS: The eIF4E gene is amplified and overexpressed in HNSCC. Amplification and elevation of eIF4E were highest in the tumor core, intermediate in the transition zone, and lowest in the tumor-free margin. There appears to be progression of eIF4E gene amplification and overexpression from the "tumor-free" margin to the tumor core.     

Care during menopause: comparison of a women's health practice and traditional care

Despite the growth in primary care-based women's health centers, little is known about the characteristics of women's health patients and the quality of care provided in women's health centers versus traditional practices. Our objective was to compare a women's health practice and a general internal medicine practice on issues of care during menopause. A cross-sectional survey was administered simultaneously to patients aged 50-70 and their primary care physicians in a women's health practice and an affiliated general internal medicine practice. The survey asked patients about health behaviors, past and current hormone use, menopausal symptoms, and attitudes about menopause. Physicians were asked to estimate their patients' attitudes. Patients in women's health practices were younger, more likely to be smokers, and more likely to have had a prior hysterectomy. Women's health patients were somewhat more likely to report concerns related to menopausal symptoms. Women's health patients and patients attending the general internal medicine practice reported similar rates of past or current use of hormone therapy, after adjusting for prior hysterectomy and age. Physicians in women's health and general medicine were similar in their ability to estimate their patients' attitudes. In the general internal medicine practice, female physicians tended to better estimate their patients' attitudes than their male colleagues. Patients seeking care in a women's health practice differed in symptoms and concerns about the menopause compared with patients in a traditional primary care setting. Physicians' understanding of patients' menopausal concerns did not differ between the two practices. However, there may be gender differences in physicians' understanding of patients' concerns.     

Mononuclear cell proliferation and hyperplasia during Wallerian degeneration in the visual system of the goldfish in the presence or absence of regenerating optic axons

Patterns of proliferation and changes in non-neuronal cell number in the visual system of the goldfish have been quantitatively examined during optic axon regeneration after an optic nerve crush (ONC). In addition, in order to examine the effect of the regenerating axons on cellular responses in the visual pathways, we did a similar analysis of animals with the right eye removed (ER). Finally, we used double labeling protocols to demonstrate that the proliferating cells that we were counting were mostly phagocytic cells of the mononuclear lineage. In animals with an ONC, we observed an early burst of proliferation that peaked between 7 and 14 days after surgery in all parts of the visual system. In the optic tract, there was also a secondary rise that peaked at 21 days. Levels of proliferation returned to normal by 32 days postoperative in the tract and tectum, while they remained somewhat elevated in the optic nerve for at least 93 days. The total number of non-neuronal cells in the visual paths also rose to peak values between 7 and 14 days after ONC surgery. In the optic tract and tectum, the values fell rapidly after this time, while in the optic nerve, there was a secondary peak at 32 days after which values remained elevated for the duration of the experiment. As compared to animals with an ONC, enucleation resulted in elevated proliferation and hyperplasia at early postoperative intervals. However, because these differences occurred when axons had not yet regenerated into the affected structures, these data do not provide strong evidence for a direct effect of regenerating optic axons on the early cellular responses during Wallerian degeneration in the goldfish. In addition, in the tectum, there was an early increment in cell number that was not associated with elevated levels of proliferation. We believe that this increment represents immigration of resident microglia from other regions of the brain.     

The relationship between urban environment and the inflammatory bowel diseases: a systematic review and meta-analysis

ABSTRACT: BACKGROUND: The objective of this study was to conduct a systematic review with meta-analysis of studies assessing the association between living in an urban environment and the development of the Crohn's disease (CD) or ulcerative colitis (UC). METHODS: A systematic literature search of MEDLINE (1950-Oct. 2009) and EMBASE (1980-Oct. 2009) was conducted to identify studies investigating the relationship between urban environment and IBD. Cohort and case-control studies were analyzed using incidence rate ratio (IRR) or odds ratio (OR) with 95 % confidence intervals (CIs), respectively. Stratified and sensitivity analyses were performed to explore heterogeneity between studies and assess effects of study quality. RESULTS: The search strategy retrieved 6940 unique citations and 40 studies were selected for inclusion. Of these, 25 investigated the relationship between urban environment and UC and 30 investigated this relationship with CD. Included in our analysis were 7 case-control UC studies, 9 case-control CD studies, 18 cohort UC studies and 21 cohort CD studies. Based on a random effects model, the pooled IRRs for urban compared to rural environment for UC and CD studies were 1.17 (1.03, 1.32) and 1.42 (1.26, 1.60), respectively. These associations persisted across multiple stratified and sensitivity analyses exploring clinical and study quality factors. Heterogeneity was observed in the cohort studies for both UC and CD, whereas statistically significant heterogeneity was not observed for the case-control studies. CONCLUSIONS: A positive association between urban environment and both CD and UC was found. Heterogeneity may be explained by differences in study design and quality factors.