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Carlton Johnson, et al., v. Webb Thompson, M.D., et al. Petition for a Writ of Certiorari to the United States Court of Appeals for the Tenth Circuit.
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Diagnosis and surgical treatment of a nasopharyngeal cyst in a dog.
A 21-month-old boxer dog was presented with clinical signs caused by nasopharyngeal obstruction. A mineralised mass in the nasopharynx was identified by radiography. Computed tomography allowed accurate anatomical localisation of the cystic lesion and identification of an ossified wall. Surgical removal of the mass by a ventral approach resulted in complete resolution of clinical signs. Histopathological examination strongly suggested that the cyst was derived from remnants of Rathke's pouch.
Assessment of potential for cancer control by Golden State Medical Association physicians.
To gather data on which to base the design of an intervention program to decrease cancer mortality in the black population of California, physician members of the Golden State Medical Association were surveyed to determine their current practices relating to early cancer detection and cancer prevention. Respondents' estimates of the proportions of their patients in various categories indicated that at least 60% to 70% of their patients were potential subjects for intensive early cancer detection and cancer prevention efforts. Thirty-four percent of respondents reported that they were performing early cancer detection examinations on all their patients. On the average, respondents estimated that about 70% of their patients (more than 80% of patients of primary care physicians) were receiving either routine check-ups or specific early cancer detection examinations. Patient education about various aspects of cancer and cancer prevention emerged as the most readily attainable means to reduce cancer mortality in blacks. It was most frequently mentioned both as something that physicians could do to help achieve this goal and as an outside resource physicians would find useful in their practices. Its lack was cited as the greatest barrier to early cancer detection and cancer prevention in the black population.
In situ lymphoproliferation in renal transplant biopsies.
A double immunohistochemical labelling procedure in paraffin-embedded renal tissue is reported in which CD3 was targeted as a T cell marker and Ki67 as a marker of cell proliferation. Proliferating and quiescent T cells were unequivocally identified in situ, and their precise location within the kidney was clarified by the use of periodic acid-Schiff counterstaining to outline the basement membranes. Proliferating tubular epithelial cells were also clearly identified. The results showed that T lymphocytes proliferate within the tubular compartment during acute renal allograft rejection. Preliminary evaluation of the method in routine transplant biopsies indicated significant correlations between histologically defined rejection grade and mean intratubular T lymphocytes per tubular cross section and between proliferation of tubular epithelial cells and of intratubular T lymphocytes. The associated tubular epithelial cell proliferation may be a response to local damage.
Single soleus muscle fiber function after hindlimb unweighting in adult and aged rats.
This investigation compared how hindlimb unweighting (HU) affected the contractile function of single soleus muscle fibers from 12- and 30-mo-old Fischer 344 Brown Norway F1 Hybrid rats. After 1 wk of HU, functional properties of single permeabilized fibers were studied, and, subsequently, the fiber type was established by myosin heavy chain (MHC) analysis. After HU, the relative mass of soleus declined by 12 and 19% and the relative mass of the gastrocnemius declined by 15 and 13% in 12- and 30-mo-old animals, respectively. In 12-mo-old animals, the peak active force (5.0 +/- 0.2 x10(-4) vs. 3.8 +/- 0.2 x10(-4) N) and the peak specific tension (92 +/- 4 vs. 78 +/- 3 kN/m2) were significantly reduced in the MHC type I fibers by 24 and 15%, respectively. In 30-mo-old animals, the peak active force declined by 40% (4.7 +/- 0.2 x10(-4) vs. 2.8 +/- 0. 3 x10(-4) N) and the peak specific tension declined by 30% (79 +/- 5 vs. 55 +/- 4 kN/m2). The maximal unloaded shortening velocity of the MHC type I fibers increased in 12-mo-old animals (from 1.65 +/- 0.12 to 2.59 +/- 0.26 fiber lengths/s) and in 30-mo-old animals (from 0.90 +/- 0. 09 to 1.50 +/- 0.10 fiber lengths/s) after HU. Collectively, these data suggest that the effects of HU on single soleus skeletal muscle fiber function occur in both age groups; however, the single MHC type I fibers from the older animals show greater changes than do single MHC type I fibers from younger animals.
Effects of secretin on guanyl cyclase of various tissues.
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The Scott wiring technique for direct repair of lumbar spondylolysis.
Between 1979 and 1989, we treated 22 patients with symptomatic lumbar spondylolysis which had not responded to conservative treatment by a modified Scott wiring technique to give direct repair of the lytic defects with stabilisation. The patients' mean age at the time of operation was 15 years; the mean follow-up period was four years. All 19 patients under 25 years old had satisfactory results. Two of the three patients over 25 years old had poor results. The age of the patient at surgery seems to be an important determinant of outcome. Radiologically confirmed fusion is of secondary importance. The presence of a grade I spondylolisthesis did not prejudice the result. We recommend the Scott wiring technique to stabilise the direct repair of a lumbar spondylolysis.
Evaluation of the in vivo function of the Hancock porcine xenograft in the aortic position.
We evaluated the vivo hemodynamic function of the stent-mounted glutaraldehyde-fixed porcine xenograft in 23 patients who had undergone aortic valve replacement from 2 days to 24 months prior to the study. Functional aortic valve orifice areas for the porcine xenograft ranged from 0.58 to 3.0 sq. cm., the average area being 1.36 sq. cm. Six patients had calculated prosthetic valve orifice areas less than 1.0 sq. cm. Valve orifice area did not correlate significantly with valve size or the time interval from surgery to postoperative study. Left ventricular stroke volume showed a significant, positive correlation with calculated xenograft orifice area. Systemic thromboembolism was not encountered. One patient required reoperation for xenograft stenosis caused by dense fibrin deposition on the aortic leaflets. We conclude that use of the stent-mounted glutaraldehyde-fixed porcine xenograft can be associated with significant functional stenosis which may be related to annulus size or inertial properties of the valve. These factors should be taken into consideration when considering use of the stent-mounted glutaraldehyde-fixed porcine xenograft in individual patients.
Use of green fluorescent protein to assess urease gene expression by uropathogenic Proteus mirabilis during experimental ascending urinary tract infection.
Proteus mirabilis, a cause of complicated urinary tract infection, expresses urease when exposed to urea. While it is recognized that the positive transcriptional activator UreR induces gene expression, the levels of expression of the enzyme during experimental infection are not known. To investigate in vivo expression of P. mirabilis urease, the gene encoding green fluorescent protein (GFP) was used to construct reporter fusions. Translational fusions of urease accessory gene ureD, which is preceded by a urea-inducible promoter, were made with gfp (modified to express S65T/V68L/S72A [B. P. Cormack et al. Gene 173:33-38, 1996]). Constructs were confirmed by sequencing of the fusion junctions. UreD-GFP fusion protein was induced by urea in both Escherichia coli DH5alpha and P. mirabilis HI4320. By using Western blotting with antiserum raised against GFP, expression level was shown to correlate with urea concentration (tested from 0 to 500 mM), with highest induction at 200 to 500 mM urea. Fluorescent E. coli and P. mirabilis bacteria were observed by fluorescence microscopy following urea induction, and the fluorescence intensity of GFP in cell lysates was measured by spectrophotofluorimetry. P. mirabilis HI4320 carrying the UreD-GFP fusion plasmid was transurethrally inoculated into the bladders of CBA mice. One week postchallenge, fluorescent bacteria were detected in thin sections of both bladder and kidney samples; the fluorescence intensity of bacteria in bladder tissue was higher than that in the kidney. Kidneys were primarily infected with single-cell-form fluorescent bacteria, while aggregated bacterial clusters were observed in the bladder. Elongated swarmer cells were only rarely observed. These observations demonstrate that urease is expressed in vivo and that using GFP as a reporter protein is a viable approach to investigate in vivo expression of P. mirabilis virulence genes in experimental urinary tract infection.
Transseptal and retrograde left ventricular catheterization in patients with the stent-mounted porcine xenograft valve prosthesis in the aortic position.
Cardiac catheterization techniques for measuring the systolic pressure gradient across the stent-mounted porcine xenograft in the aortic position and accomplishing left ventriculography are described. The transseptal technique is a rapid and predictable means of entering the left ventricle but requires a highly skilled operator. Retrograde left ventricular catheterization via the femoral artery is a technique familiar to all invasive cardiologists. Usually a pitfall catheter is used. In patients with the stent-mounted procine xenograft in the aortic position, we have found the A2 Multipurpose catheter to be the fastest and most predictable means of entering the left ventricle from the groin. Potential complications of retrograde left ventricular catheterization in patients with aortic valve prostheses are discussed.
Value of attenuation correction on ECG-gated SPECT myocardial perfusion imaging related to body mass index.
BACKGROUND: Obesity is a growing problem in the United States, and attenuation artifacts are more prevalent in this patient group. This study evaluated the impact of attenuation correction in patients with a high body mass index (BMI). METHODS AND RESULTS: Three readers interpreted gated attenuation-corrected and non-attenuation-corrected rest/stress technetium 99m sestamibi myocardial perfusion imaging results in 116 patients (BMI <30, n = 60; BMI > or =30, n = 56) who had coronary angiography no more than 60 days after imaging. Readers were blinded to all clinical information and as to whether myocardial perfusion imaging was attenuation-corrected or non-attenuation-corrected. Sensitivity, specificity, and accuracy for detection of coronary artery disease of 70% or greater for attenuation-corrected versus non-attenuation-corrected single photon emission computed tomography (SPECT) were 86% versus 89%, 79% versus 50%, and 84% versus 79%, respectively. Sensitivity, specificity, and accuracy for attenuation-corrected versus non-attenuation-corrected SPECT for patients with BMI less than 30 were 90% versus 90%, 82% versus 64%, and 88% versus 85%, respectively. For BMI of 30 or greater, the results were 82% versus 87%, 76% versus 41%, and 80% versus 73%, respectively. There was a significant difference in specificity overall ( P = .02) and for the category of BMI of 30 or greater ( P = .03). CONCLUSIONS: This study demonstrates that electrocardiography-gated attenuation-corrected Tc-99m sestamibi SPECT myocardial perfusion imaging improves specificity compared with electrocardiography-gated non-attenuation-corrected SPECT myocardial perfusion imaging, especially in patients with BMI of 30 or greater.
Reversible control of oestradiol-stimulated growth of MCF-7 tumours by tamoxifen in the athymic mouse.
We investigated the ability of high concentrations of oestradiol to reverse the growth inhibitory action of tamoxifen on MCF-7 breast cancer cells in vivo. Tamoxifen inhibits the oestradiol stimulated growth of MCF-7 cells in athymic mice. Using a sustained release preparation of tamoxifen we consistently achieved serum concentrations of the drug in the 40 to 50 ng ml-1 range and much higher levels in tissues. These serum levels are sufficient to inhibit the oestrogen stimulated growth of MCF-7 tumours exposed to physiologic (i.e. 300-600 pg ml-1 serum oestradiol concentrations). However, by administering dosages that increase serum oestradiol concentrations to 900-2000 pg ml-1, mimicking the increase often observed clinically in premenopausal women taking tamoxifen, we show that the growth inhibitory action of tamoxifen can be partially reversed. Serum tamoxifen levels were elevated to nearly 400 ng ml-1 by injecting 1 mg day-1 tamoxifen (IP 3 x weekly); this dosage was more effective at inhibiting oestradiol stimulated tumour growth than subcutaneous tamoxifen capsules alone. Our data suggest that at low serum levels tamoxifen may not act optimally. There may be a need to monitor tamoxifen levels in premenopausal patients to ensure that they are high enough not to be overcome by a tamoxifen induced increase in ovarian steroidogenesis.
Prognostic implications of the tall cell variant of papillary thyroid carcinoma.
The tall cell variant (TCV) of papillary thyroid carcinoma, characterized by a population of tall columnar cells with a height at least twice the width, was analyzed in 12 patients and compared to tumors from 12 patients with the usual type of papillary thyroid carcinoma (UPTC) matched for age, sex, and date of diagnosis to determine if tall cell histology had prognostic significance. Patients with TCV had significantly higher incidences of extrathyroidal disease, recurrent disease, and metastases compared to patients with UPTC. TCV patients also died of their tumors more frequently than UPTC patients (3/12 versus 0/12). There was no significant difference in tumor size or in the incidence of cervical lymph node involvement between the patient groups. These results show that TCV of papillary thyroid carcinoma has a more aggressive clinical course and a worse prognosis than UPTC in patient groups with similar age and sex distribution, length of follow-up, and tumor size.
Thrombin activity resides on LVAD Dacron inflow and outflow grafts.
Patients on left ventricular assist devices (LVADs) are at increased risk for thromboembolism, and they experience elevations in platelet release and thrombin activity indices during device implantation. The Dacron grafts that lead from the ventricle to the LVAD and back to the aorta may harbor thrombin activity and protect this thrombin from anticoagulant action. To investigate this possibility, specimens isolated from LVAD grafts at the time of device explantation or implantation were incubated with citrated platelet poor plasma (cPPP), cPPP and 2 U/ml of heparin, cPPP and 2 U/ml of recombinant hirudin (r-hirudin), or cPPP and 50 U/ml of heparin. Thrombin activity was measured by the increase in incubated cPPP fibrinopeptide A (FPA) concentrations over cPPP FPA levels, without material contact. A chromogenic substrate for thrombin verified the effects seen. Thrombin activity was found at comparable levels on both the inflow and outflow LVAD grafts at explantation. This activity was not inhibited by low concentrations of heparin, but 50 U/ml of heparin and 2 U/ml of r-hirudin reduced the activity. At graft implantation (after preclotting), thrombin activity was higher than at explantation, but susceptibility to inhibition by heparin was also significantly greater. These results confirm that the LVAD Dacron grafts harbor surface thrombin activity resistant to anticoagulation that may be a primary source for LVAD thrombogenicity.
OBSERVED EFFECTS OF UREA ON PYELONEPHRITIS.
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Enhancement of peroxynitrite-induced apoptosis in PC12 cells by fibroblast growth factor-1 and nerve growth factor requires p21Ras activation and is suppressed by Bcl-2.
Extracellular trophic factors can regulate whether cells subjected to oxidative stress will survive to proliferate or else undergo cell death. We have previously shown that about 35% of undifferentiated PC12 cells undergo apoptosis 18 h after exposure to peroxynitrite and that pretreatment with nerve growth factor (NGF) protects PC12 cells through activation of phosphatidylinositol (PI) 3-kinase. In contrast, pretreatment with acidic fibroblast growth factor (FGF-1) approximately doubled apoptosis. We report here that NGF added immediately after peroxynitrite treatment no longer protected against apoptosis, but instead enhanced apoptosis to the same extent as FGF. We further investigated which signaling pathways were involved in increasing the level of apoptosis. Overexpression of Bcl-2 blocked the increased apoptosis caused by NGF and FGF-1, but Bcl-2 did not prevent the induction of apoptosis by peroxynitrite alone. The increase in apoptosis caused by the trophic factors was also blocked by the expression of a dominant negative p21Ras mutant. Activation of PI 3-kinase by NGF pretreatment completely protected against both the enhanced apoptosis induced by FGF-1 pretreatment and NGF posttreatment and the apoptosis induced by peroxynitrite alone. Our results indicate that the enhancement of peroxynitrite-induced apoptosis caused by NGF and FGF-1 is dependent on the stimulation of a proapoptotic pathway involving p21Ras that can be suppressed by Bcl-2.
Inner city primary care providers' breast cancer screening knowledge: implications for intervention.
Low income and minority women continue to have relatively low breast cancer screening rates. Since physician recommendation is one of the most important determinants of mammography participation, we aimed to characterize the breast cancer screening knowledge of primary care providers serving a socially disadvantaged population. The study was conducted at the Adult Medicine Clinic of Seattle's county hospital. All attending physicians, resident physicians, and mid-level practitioners were asked to complete a questionnaire in the spring of 1995. Forty-nine of 52 (94%) eligible providers completed the survey. The respondents generally agreed with published guidelines for screening mammography use. In contrast, they had relatively low levels of knowledge about breast cancer risk factors and the effectiveness of other breast cancer screening methods. Additionally, providers tended to over-estimate their breast cancer screening knowledge and skills. For example, 69% believed that they could answer patients' questions about mammography, but only 23% were aware of Medicaid's reimbursement policy for the procedure. For some variables, attending physicians were no more knowledgeable than resident physicians. Our results reinforce the need for increased preventive care training in medical schools and primary care residency programs. Educational programs for providers serving disadvantaged populations might usefully focus on pragmatic issues such as institutional costs and public payer reimbursement policies.