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.     

ImmunoCyt/uCyt+ improves the sensitivity of urine cytology in patients followed for urothelial carcinoma.

ImmunoCyt/uCyt is a fluorescent test combining three monoclonal antibodies. In this study, it has been tested as a complement to cytology in the detection of urothelial carcinoma in urine. It has been performed simultaneously with standard cytology and cystoscopy on 870 urine analyses from one hospital. In 136 cases, one or more bladder tumors were found. Overall sensitivity of cytology, ImmunoCyt/uCyt and combined analyses reached 29, 74 and 84%, respectively, and overall specificity was 98, 62 and 61%. The negative predictive value of cytology, ImmunoCyt/uCyt and both analyses was 88, 93 and 95%, respectively, and the positive predictive value was 70, 26 and 29%. The sensitivity of cytology for low malignant potential neoplasms, low- and high-grade papillary carcinomas was 6, 18 and 53%, while it reached 71, 79 and 93% when combined with ImmunoCyt/uCyt. The sensitivity of cytology for stages Ta, T1, T2 and over and Tis tumors was 12, 67, 47 and 50%, while it reached 78, 83, 79 and 100% when combined with ImmunoCyt/uCyt. In the absence of tumor on cystoscopy but with positive ImmunoCyt/uCyt, 18% of patients developed a tumor, 2-6 months later. Of the 109 cases diagnosed as suspicious for malignancy by cytology, a tumor was present in 30 cases and ImmunoCyt/uCyt was positive in 22 (73%) of them. In conclusion, ImmunoCyt/uCyt may be used to postpone cystoscopies in patients followed for bladder cancer and may help to save cytologist and pathologist screening time.     

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.     

Candida albicans osteomyelitis of the spine: progressive clinical and radiological features and surgical management in three cases

Candida albicans vertebral osteomyelitis is rare. Three cases are presented. Without antifungal treatment, they developed spinal collapse and neurological deterioration within 3–6 months from the onset of symptoms. There was a delay of 4.5 and 7.5 months between the onset of symptoms and surgery. All patients were managed with surgical debridement and reconstruction and 12-week fluconazole treatment. The neurological deficits resolved completely. The infection has not recurred clinically or radiologically at 5–6 years follow-up. Although rare, Candida should be suspected as a causative pathogen in cases of spinal osteomyelitis. Without treatment the disease is progressive. As soon as osteomyelitis is suspected, investigations with MRI and percutaneous biopsy should be performed followed by medical therapy. This may prevent the need for surgery. However, if vertebral collapse and spinal cord compression occurs, surgical debridement, fusion and stabilisation combined with antifungal medications can successfully eradicate the infection and resolve the neurological deficits.     

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.