Academic Degrees and Clinical Practice Characteristics: The University of Washington Physician Assistant Program: 1969-2000

CONTEXT: The physician assistant profession has been moving toward requiring master's degrees for new practitioners, but some argue this could change the face of the discipline. PURPOSE: To see if there is an association between physician assistants' academic degrees and practice in primary care, in rural areas, and with the medically underserved. METHODS: Surveys were sent to 880 graduates of the first 32 University of Washington physician assistant classes through 2000. Respondents noted their academic degree at program entry and the highest degree attained at any time up to the time of survey. Relationships between practice characteristics and academic degree levels were tested by unadjusted odds ratios and logistic regression after controlling for year of graduation and sex. RESULTS: Of the 478 respondents, 54% worked in primary care, about 30% practiced in nonmetropolitan communities, and 42% reported providing care for the medically underserved. Respondents with no degree (33% of total at entry, 24% at survey) were significantly more likely than degree holders to work in primary care and nonmetropolitan areas. Respondents with no degree at program entry were significantly more likely, and those with no degree at the time of the survey were marginally more likely, to self-report work with the medically underserved. CONCLUSION: Respondents with no academic degree are significantly more likely to demonstrate a commitment to primary, rural, and underserved health care. These findings may inform the national debate about the impact of required advanced degrees on the practice patterns of nonphysician providers.     

Do forceps biopsies truthfully reflect the nature of endoscopically uncovered polypoid lesions of the colon?

BACKGROUND: Total excision of colonic polyps is not always attainable and in some patients it is clinically contraindicated. Also, a resected polyp may be lost at any step between its endoscopic removal and its embedding in paraffin. The aim of this study was to compare the histological features of colonic polyps as analysed by the study of biopsy-forceps obtained samples with those assessed on scrutinizing the totally resected growths. PATIENTS AND METHODS: This prospective study included a cohort of 59 patients in whom, in the course of an elective colonoscopy, a total excision of a 6 mm-sized or larger polyp was called for. Sizeable biopsies were obtained by means of an Olympus Multibyte forceps prior to the total polypectomy. Subsequent to the study of the polypectomy specimens, the forceps biopsy samples were submitted for histological examination. The pathologists were blinded as to the source of the tissue they were studying. The diagnoses rendered by evaluating the biopsy samples and polypectomy specimens of each patient were contrasted with each other. RESULTS: Major discrepancies between the histological features of the fragments captured by the biopsy-forceps and the factual nature of the totally removed polyps were uncovered in 11 (18.6%) of 59 cases. Intriguingly, the grade of the tumours was underrated in all the 11 cases, as judged by contrasting the tentative diagnoses of the forceps-biopsies with the decisive diagnoses of the polypectomies. Importantly, 2 adenocarcinomas would have been missed by just looking at the forceps-retrieved sample. CONCLUSIONS: In our experience, a discordance of 18.6% is to be expected between the diagnoses rendered after examining forceps-biopsies of and totally excised colonic polyps. Nevertheless, it is advisable to procure biopsies prior to the excision of the growths, because on those occasions in which patients' growths cannot be removed or have not been retrieved for one reason or another, a small forceps-captured tissue sample correctly reflects the characteristics of the polyp in 81.4% of the cases. Finally, the biopsies may be discarded in the event that total removal was successful.     

Heightened risk of breast cancer following pregnancy: could lasting systemic immune alterations contribute?

The protective effect of having a first full-term pregnancy (FFTP) at a younger age on women's lifetime risk of breast cancer is well known. Less appreciated is the increased risk seen in the years immediately following pregnancy. This adverse effect is more pronounced and more prolonged in women with later age at FFTP. The mechanisms responsible for this increased risk are still poorly understood. In the present paper, we put forward the hypothesis that the marked peripheral immune changes induced by pregnancy may account for these effects. We highlight immune changes that characterize the unique immune state of pregnancy (a combination of cellular immunosuppression and enhanced inflammatory response), note the resemblance of these changes to cancer escape mechanisms, and discuss why such immune changes may be critical for the development of breast cancer following pregnancy. We further support this idea by initial findings from our own laboratory that the age at FFTP is negatively related to natural killer cell cytotoxicity many years later and propose possible models for the kinetics of the immune changes during and following pregnancy. The effect of age at FFTP on the immune function is currently understudied. Its potential relevance to the development of breast cancer stresses the need for further research.     

Comparison of murex single-use diagnostic system with traditional enzyme immunoassay for detection of exposure to human immunodeficiency virus.

Because a retrospective study detected 13 negative Western blots out of 38 single-use diagnostic system (SUDS)-positive cases over a 1-year period, we performed a prospective study to compare the performance of the SUDS test with that of enzyme immunoassay (EIA). Of 888 SUDS-tested sera, 875 (98.4%) were both SUDS and EIA negative and 5 (0.6%) were SUDS, EIA, and Western blot positive. The rate of SUDS-positive samples decreased from 3.16/month in the retrospective study to 1.33/month in the prospective study. The immunoassays had sensitivities and specificities of 100 and 99.7 (SUDS) and 100 and 99.4% (traditional EIA), respectively. In laboratories with experienced personnel, the SUDS test performs as well as the EIA as a screen for infection with the human immunodeficiency virus.     

大鼠外侧隔核的传出纤维联系

用HRP、WGA—HRP及CB—HRP法顺行追踪了大鼠外侧隔核的传出纤维联系。结果表明外侧隔核发生较多的纤维经内侧前脑束投射到下丘脑;经丘脑髓纹投射到丘脑带旁核、双侧内侧缰核,也有少量纤维投射到外侧缰核,外侧隔核向扣带皮质的投射主要终止在扣带皮质前部,少量纤维投射到后部。此外,有少量纤维投射到杏仁中央核、杏仁内侧核、中缝背核、中央灰质腹、外侧部、被盖腹侧区、脚间核及蓝斑等。     

The effect of tyrphostin AG-556 on intimal thickening in a mouse model of arterial injury

BACKGROUND: Inflammation has been shown to play an important role in promoting the response to arterial injury and proinflammatory cytokines, such as tumor necrosis factor (TNF) alpha, are candidate mediators. AG-556 is a tyrosine kinase inhibitor proven to be effective in a model of multiple sclerosis-like syndrome in mice due to its immunomodulating effect. In the current study, we investigated the effect of the tyrphostin AG-556 on neointimal thickening and cytokine profile in a model of arterial injury in the mouse. METHODS: Injury was induced by external cuff placement on the left femoral artery of wild-type C57BL/6 mice. AG-556 dissolved in DMSO was injected intraperitoneally daily to the injured mice in a dosage of 2 mg/mouse. Control mice received DMSO injections. Histological analysis was carried out to assess neointimal formation. Splenocytes were cultured in the absence and presence of a mitogen for evaluation of thymidine incorporation and cytokine production. RESULTS: AG-556 treatment significantly attenuated intimal thickening (43,000+/-17,000 microm2; n=11) when compared to DMSO administration (286,000+/-127,000 microm2; n=10; P<0.05). Basal interferon-gamma production by splenocytes from AG-556-treated mice was increased by approximately 20-fold in comparison with levels in DMSO-treated animals, whereas Con-A induced secretion of the cytokine was similar between both groups. Levels of TNF-alpha, IL-4 and IL-10 in the culture supernatant from treated and non-treated animals did not differ significantly. CONCLUSION: The tyrosine kinase inhibitor AG-556 may have a role in the reduction of intimal thickening. The effect could be mediated via an immune modulating effect involving a significant increase in the smooth muscle cell inhibitory cytokine IFN-gamma.     

Effect of IL-2-Bax, a novel interleukin-2-receptor-targeted chimeric protein, on bleomycin lung injury

The role of lymphocytes in the pathogenesis of lung fibrosis is not clear, but the weight of the evidence supports a pro-fibrotic effect for lymphocytes. The high-affinity interleukin-2 receptor (haIL-2R) is expressed on activated, but not quiescent, T lymphocytes. This selective expression of haIL-2R provides the basis for therapeutic strategies that target IL-2R-expressing cells. We hypothesized that elimination of activated lymphocytes by IL-2R-targeted chimeric proteins might ameliorate lung fibrosis. We investigated the effects of IL-2-Bax, a novel apoptosis-inducing IL-2R-targeted chimeric protein, on bleomycin-induced lung injury in mice. Treatment groups included (i) a single intratracheal instillation of bleomycin and twice-daily intraperitoneal injections of IL-2-Bax; (ii) intratracheal bleomycin and intraperitoneal IL-2-PE66(4Glu), an older-generation chimeric protein; (iii) intratracheal bleomycin/intraperitoneal PBS; (iv) intratracheal saline/intraperitoneal PBS. Lung injury was evaluated 14 days after intratracheal instillation by cell count in bronchoalveolar lavage (BAL) fluid, semi-quantitative and quantitative histomorphological measurements and by biochemical analysis of lung hydroxyproline. Bleomycin induced a BAL lymphocytosis that was significantly attenuated by IL-2-Bax and IL-2-PE66(4Glu). However, morphometric parameters and lung hydroxyproline were unaffected by the chimeric proteins. These results show that IL-2-Bax reduces the lymphocytic infiltration of the lungs in response to bleomycin, but this effect is not accompanied by a decrease in lung fibrosis.     

大鼠下丘脑一氧化氮合酶（NOS）阳性神经元的分布

观察大鼠下丘脑各核团NOS阳性神经元的分布。采用还原型尼克酰胺腺嘌呤二核苷酸脱氢酶（NADPH－d）法，结果显示，大量NOS阳性神经元见于下丘脑外侧区、视上核（SO）和室旁核（Pa）；出现较多NOS阳性神经元的部位是视前大细胞核，见到少量NOS阳性神经元的部位是室周核、视前内侧区、视前外侧区和下丘脑前区。结论：NOS阳性神经元分布于下丘脑的许多核团。     

大鼠膈神经传出和传入神经成分在脊髓内的分布

采用HRP追踪法,对成年大鼠膈神经运动纤维的起源和初级传入神经元胞体的位置及在其中枢突脊髓的投射进行了观察。结果表明,膈神经运动纤维在脊髓标记(膈核)主要分布在注射侧C_3-C_5脊髓节段的前角。隔神经感觉纤维初级传入标记的神经元见于注射侧C_3-C_6后根节,其中C_4标记的细胞数最多。