Provider-sponsored networks top priority.
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Community Networks↗
Biomedical subjects
D E Johnson
Publications and source records attributed to D E Johnson.
Providers must adapt fast to risk contracting.
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Capitation Fee↗
GPOs and materials managers must adapt to integrated systems.
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Cost Allocation↗
Facility planning for small and rural hospitals.
As changes in health care delivery move faster than ever, small or rural hospitals are struggling in a catch-up mode. In order to reverse this trend, these facilities need to reassess their position in the marketplace and develop a flexible plan for responding to the needs. This document provides a model to help achieve the vision of the physical plant in its supporting role to the strategic vision for the hospital, as well as options in the business of caring in a variety of alternative caregiving and treatment environments.
Decision Making, Organizational↗
Recombinant human retinoblastoma protein inhibits cancer cell growth.
Aberrant expression of the tumor suppressor gene RB1 is associated with a variety of solid tumors and hematopoietic neoplasms. Certain cancer cell lines in which the protein encoded by RB1 (p110RB) is absent have been reported to show decreased growth rate, clonogenicity, or tumorigenicity following insertion of a transcriptionally active RB1 gene. We asked whether these RB-deficient cells could be growth inhibited by direct exposure to purified p110RB. We report a decrease in uptake of tritiated thymidine by 5637 bladder carcinoma cells (RB-negative) when purified recombinant p110RB is added to culture media. Internalization of the protein by cells and translocation to the nucleus are demonstrated by immunohistochemistry, FACS, and detection of radiolabeled protein in subcellular fractions. Next, we chose a well-described leukemia cell culture model to investigate the potential effect of recombinant p110RB in clinical disease. We observed dose-related decreases in cell number of colony formation in vitro in 8 of 20 acute myelogenous leukemia samples, 7 of which did show endogenous p110RB detectable by immunohistochemistry. Histological appearance following exposure to p110RB shows cytoplasmic vacuolization and nuclear lobulation of degenerating cells. We conclude that purified p110RB added to culture media is internalized by cells, translocated to the nucleus, and exerts a growth-inhibitory effect on certain cancer cell types.
Acute Disease↗
Implication of cell kinetic changes during the progression of human prostatic cancer.
The daily percentage of cells proliferating and dying were determined for normal, premalignant, and cancerous prostatic cells within the prostate as well as for prostatic cancer cells in lymph node, soft tissue, and bone metastases from untreated and hormonally failing patients. These data demonstrate that normal prostatic glandular cells have an extremely low but balanced rate of cell proliferation and death (i.e., both <0.20%/day). This results in a steady-state, self-renewing condition in which there is no net growth, although the glandular cells are continuously being replaced (i.e., turnover) every 500 +/- 79 days. Transformation of these cells into high-grade prostatic intraepithelial neoplastic cells initially involves an unbalanced increase in the daily percentage of cells proliferating versus dying, such that net continuous growth occurs (i.e., mean doubling time, 154 +/- 22 days). As these early proliferation lesions continue to grow into late stage high-grade prostatic intraepithelial neoplastic cells, the daily percentage of cells dying increases further to a point equaling the daily percentage of proliferation. This results in cessation of net growth while inducing a 6-fold increase in the turnover time of these cells (i.e., 56 +/- 12 days), increasing their risk of further genetic changes. The transition of late stage high-grade prostatic intraepithelial neoplastic cells into localized prostatic cancer cells involves no further increase in proliferation but a decrease in death resulting in net continuous growth of localized prostatic cancers with a mean doubling time of >/=475 days. As compared to localized prostatic cancer cells, metastatic prostatic cancer cells within lymph nodes or bones of untreated patients have an increase in daily rate of proliferation coupled with a reduction in their daily percentage of cell death, producing net growth rates with a mean doubling time of 33 +/- 4 days and 54 +/- 5 days, respectively. Remarkably, there is no further increase in proliferation in hormonally failing patients, but instead an increase in the daily percentage of androgen-independent prostatic cancer cells dying within soft tissue or bone metastases. These changes result in doubling times which are two to three times longer (i.e., 126 +/- 21 and 94 +/- 15 days) in these lymph node and bone metastatic sites, respectively, compared to similar sites in hormonally untreated patients. These data demonstrate that the daily percentage of proliferation for either androgen-dependent or -independent metastatic prostatic cancer cells is remarkably low (i.e., <3. 0%/day), consistent with why antiproliferative chemotherapy has been of such limited value against such metastatic cells. These results also suggest that prostatic carcinogenesis starts in the second to third decade of life and may require over 50 years for progression to pathologically detectable metastatic disease.
Cell Cycle↗
Altered protoxin activation by midgut enzymes from a Bacillus thuringiensis resistant strain of Plodia interpunctella.
Processing of Bacillus thuringiensis protoxins to toxins by midgut proteinases from a strain of the Indianmeal moth, Plodia interpunctella (Hubner), resistant to B. thuringiensis subspecies entomocidus (HD-198) was slower than that by midgut proteinases from the susceptible parent strain or a strain resistant to B. thuringiensis subspecies kurstaki (HD-1, Dipel). Midgut extracts from entomocidus-resistant insects exhibited five-fold lower activity toward the synthetic substrate alpha-N-benzoyl-DL-arginine rho-nitroanilide than extracts from susceptible or kurstaki-resistant insects. Midgut enzymes from susceptible or kurstaki-resistant insects converted the 133 kDa CryIA(c) protoxin to 61-63 kDa proteins, while incubations with entomocidus-resistant enzymes resulted in predominantly products of intermediate size, even with increased amounts of midgut extract. The 61-63 kDa proteins were only produced by entomocidus-resistant midgut extracts after long term incubations with the protoxin. The data suggest that altered protoxin activation by midgut proteinases is involved in some types of insect resistance to B. thuringiensis.
Animals↗
A review of electron probe X-ray microanalysis studies of salivary gland cells.
Electron probe X-ray microanalysis (EPXMA) has now been successfully applied to several salivary gland preparations. This paper briefly reviews the principles underlying this technique and the specific sample preparation procedures which permit accurate measurement of elemental concentrations in the various intracellular spaces. Findings from salivary gland studies indicate that cytoplasmic and nuclear spaces of nonstimulated acinar cells have high concentrations of K and P, and low concentrations of Mg, Ca, and S; and that mature secretory granules have high concentrations of Ca and S, and relatively low concentrations of K and P. No consistent differences have been found between the elemental concentrations of mucous and serous secretory granules. In vivo and in vitro EPXMA studies of the elemental changes associated with secretory granule maturation indicate there are at least two stages in this process: an early stage during which granule S concentration increases in parallel with mass density as condensing vacuoles mature into secretory granules, and a late stage during which granule mass density and protein content increase with no further elemental concentration changes. Findings from other in vivo and in vitro studies indicate that secretory granule membranes are permeable to Na, K, and Cl ions because the granular concentrations of these elements are altered by electrochemical gradients. Recent EPXMA results indicate that cells stimulated with parasympathomimetic agonists have decreased K and Cl concentrations, and increased Na concentrations. Furthermore, the magnitude of these changes are quantitatively consistent with changes measured using radio-isotope equilibration and other techniques. In contrast, cells stimulated with the beta-adrenergic agonist, isoproterenol, have increased concentrations of Na and Cl, but unchanged K concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Fine-needle aspiration cytology of suture granulomas of the breast: a potential pitfall in the cytologic diagnosis of recurrent breast cancer.
The fine-needle aspirates of three cases of suture granulomas of the breast area following mastectomy, lumpectomy, or axillary node dissection were reviewed. The original histologic diagnoses were mucinous (colloid) carcinoma, intraductal carcinoma, and low-grade phyllodes tumor. In two patients a new nodule developed in the surgical scar, and in the third a nodule developed in the axilla 2 cm away from the scar. The cellularity of the aspirates ranged from low to moderate, and all three cases contained variable numbers of spindled cells and fragments of cellular stroma. Multinucleated giant cells characteristic of suture granulomas were absent in all cases. Abundant metachromatic amorphous background material was present in one case, which was interpreted as recurrent mucinous carcinoma. The remaining cases were interpreted as suspicious for recurrent neoplasm. Upon excision, all were suture granulomas with fibroblastic proliferation. Suture granulomas can both clinically and cytologically mimic recurrent malignancy. The predominance of spindled cells and dissimilarity to the original tumor appear to be the most helpful features to cytologically distinguish suture granuloma from recurrent carcinoma in the absence of the characteristic multinucleated giant cells.
Adult↗
Use of the holmium:YAG (Ho:YAG) laser for treatment of superficial bladder carcinoma.
This is the first North American report describing the use of the holmium:YAG (Ho:YAG) laser to treat patients with superficial bladder carcinoma. Fifteen patients, with a total of 52 recurrent superficial bladder tumors, underwent endoscopic laser photoablation of their lesions. No intraoperative or delayed complications occurred. At follow-up cystoscopy performed 3 months after lasing, four patients (27%) were without disease; eight patients (53%) had out-of-field recurrences; and three patients (20%) were classified as having in-field recurrences. We conclude that using the Ho:YAG for endoscopic treatment of patients with superficial bladder tumors is both feasible and clinically useful and that the lack of perceived pain or discomfort during lasing, as well as the lack of need for an in-dwelling urethral catheter, makes it advantageous for selected patients over conventional electroresection techniques.
Aged↗
Interstitial laser prostatectomy.
Serial gross and histopathologic examinations of the prostate following interstitial laser prostatectomy in the canine model demonstrated distinct zonal thermal changes around the entire active area of the interstitial thermal therapy (ITT) fiber. A large, well-demarcated area of acute coagulative necrosis immediately surrounded each fiber tract; beyond that were a prominent narrow peripheral zone of marked tissue disruption and an outer zone of hemorrhage. Liquefaction within these coagulative areas was evident within 24 hours, and by 4 days, each lobe of the prostate contained an irregular cavity that became lined by normal-appearing transitional epithelium and that, by 5 weeks, communicated with the prostatic urethra. These postmortem pathologic observations, similar to findings previously reported following transurethral laser prostatectomy, suggest that interstitial laser thermal therapy may provide an additional means for treating benign prostatic hyperplasia in men.
Animals↗
Pathologic changes following transurethral canine prostatectomy with a cylindrically diffusing fiber.
Transurethral laser prostatectomy was performed on eight mongrel dogs employing a cylindrically diffusing fiber delivery system and a 1.06 mu Nd:YAG laser. Each dog received 15,000 joules of laser energy delivered to the prostate in one continuous dose of 25 watts for 10 minutes. Gross and histopathologic examinations of serial sections of the prostate were performed postoperatively after intervals of 2 hours to 7 weeks. Grossly, a spherical zone of destruction averaging 2.8 cm in diameter was present in dogs except one. Histopathologic changes in the prostate consisted of acute coagulative necrosis with interstitial edema at 2 hours, becoming hemorrhagic by 24 hours. A prominent circular area of acute coagulative necrosis with progressively larger areas of liquefaction and hemorrhage was present in prostates harvested from 4 days to 1 week after lasing. Initial re-epithelization of the resulting cavity was observed at 3 weeks with nearly complete epithelialization 7 weeks after laser treatment. The simplified fiber placement and lack of postoperative complications in this small group of dogs suggest that the cylindrically diffusing fiber could offer significant advantages over laterally deflecting fibers for transurethral prostatectomies in the dog model.
Animals↗
Cellular toxicities and membrane binding characteristics of insecticidal crystal proteins from Bacillus thuringiensis toward cultured insect cells.
The pattern of in vitro toxicity of activated toxins from several classes of entomocidal inclusion genes from Bacillus thuringiensis was measured using eight established cell lines from lepidopteran insects. Protoxins representing CryIA(b), CryIA(c), and a mixture of all three CryIA toxins (subtypes a, b, and c; from B. thuringiensis subsp. kurstaki HD-1) were compared with the protoxin representing CryIC in a bioassay which measured the viability of cultured insect cells upon exposure to entomocidal toxin proteins. The responses of the various cell lines were very specific toward the individual toxin proteins. CryIC activated protoxin was toxic for cells of Manduca sexta, Plodia interpunctella, and to a lesser extent Spodoptera frugiperda. CryIA(b) and CryIA(c) proteins were toxic toward M. sexta but relatively non-toxic for P. interpunctella or S. frugiperda. The toxicity of CryIA(b), CryIA(c), and the composite CryIA activated toxins toward cells of Choristoneura fumiferana varied substantially, with the CryIA mixture being slightly more toxic than CryIA(c) alone. CryIC toxin had no effect toward C. fumiferana cells. Probit regression analysis of dose-response relationships between insect species and crystal protein composition demonstrated specific patterns of toxicity which may be related to membrane-receptor site binding by specific toxins. Membrane binding analysis of 125I-labeled CryIA(b), CryIA(c), and CryIC toxins to insect cells from three of the cell lines yielded high specific binding only with M. sexta cells toward CryIA(c) toxin. Lower levels of binding were observed with CryIA(b) and CryIC toward cells of C. fumiferana and P. interpunctella. Although relatively low binding levels for CryIC were observed with P. interpunctella cells, toxicity was high for these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Egg yolk enhances the receptiveness of zona pellucida to sperm binding.
PURPOSE: Our purpose was to test whether treatment of zona pellucida with egg yolk enhances its receptiveness to sperm binding. Hams F-10 supplemented with 0.06 g% freeze-dried egg yolk (TM) was evaluated using the hemizona assay. Ham's F-10 supplemented with 7.5% human serum served as the control medium (CM). Salt-stored zona pellucida were bisected and each matched hemizona processed in either TM or CM for the preincubation study or both hemizona processed in CM for the coincubation study. TEST yolk-treated sperm from 10 ejaculates were then incubated with the hemizona preincubated in TM and CM but coincubated in CM or coincubated with hemizona in TM and CM. RESULTS: A significantly (P < 0.02) higher number of tightly bound sperm and hemizona index for the hemizona either preincubated or coincubated in TM compared to the respective hemizonae in CM were observed.
Egg Yolk↗
Histopathologic correlates of unstable ischemic syndromes in patients undergoing directional coronary atherectomy: in vivo evidence of thrombosis, ulceration, and inflammation.
Complex coronary morphologic abnormalities with thrombus and ulceration have been recognized in acute ischemic syndromes by angiography, angioscopy, and autopsy. However, in vivo histopathologic correlates of unstable ischemic syndromes have not been described. The purpose of this study was to characterize intracoronary lesion morphologic abnormalities by analyzing specimens excised by directional atherectomy in patients with different ischemic syndromes. Tissue specimens removed by directional coronary atherectomy of primary lesions in native vessels were matched blindly to the clinical status of 130 patients representing 43% of a consecutive directional coronary atherectomy population of 300 patients; 824 specimens (range per patient 1 to 30, mean 6.3) were obtained. Clinical subgroups were prospectively classified as recent myocardial infarction (< or = 15 days, mean 6, range 1 to 15 days), 48 patients; prolonged rest angina, 34 patients; crescendo angina, 29 patients; and stable angina, 19 patients. Shavings were prospectively analyzed for presence of thrombus, ulceration, or chronic inflammatory cells. Thrombus was observed in 33 (69%) patients with recent myocardial infarction, 17 (50%) with rest angina, 12 (41%) with crescendo angina, 7 (37%) with stable angina (p = 0.048). Plaque ulceration was identified in 12 (25%) patients with recent myocardial infarction, 4 (12%) with rest angina, 2 (7%) with crescendo angina, and 1 (5%) with stable angina (p = 0.09). Inflammatory cells were noted in the specimens of 32 (67%) patients with recent myocardial infarction, 16 (45%) with rest angina, 12 (41%) with crescendo angina, and 9 (45%) with stable angina.(ABSTRACT TRUNCATED AT 250 WORDS)
Angina Pectoris↗
Orotic acid improves left ventricular recovery four days after heterotopic transplantation.
Orotic acid accelerates compensatory myocardial hypertrophy after regional ischemia and improves left ventricular function acutely after global ischemia. In this study, the effect of orotic acid on left ventricular function was investigated 4 days after global ischemia (75 minutes, 21 degrees C) using heterotopically transplanted rabbit hearts (n = 18). Experimental animals received daily 100-mg/kg doses of intraperitoneally administered orotic acid, starting 1 day before transplantation, and showed a threefold increase in the serum level of orotic acid by 4 days. After 1 hour of reperfusion, the developed pressure was equally depressed in both the control and experimental groups; however, 4 days later, the developed pressure in control animals was decreased by 3 +/- 3 mm Hg (versus the developed pressure measured at 1 hour) while the developed pressure in experimental animals was significantly increased by 25 +/- 8 mm Hg. Heterotopically transplanted hearts manifested diminished systolic function (stemming from ischemia and unloading) as well as decreased expression of adult myosin. Because orotic acid has been observed to produce an increase in protein synthesis in other models, we investigated whether this improvement in systolic function resulted from an orotic acid-mediated augmentation (or preservation) or normal adult myosin expression. Both orotic acid-treated and untreated hearts manifested decreased expression of the beta-myosin heavy chain protein and steady-state messenger RNA levels. Because function improved with decreased beta-myosin heavy chain expression, an alternate mechanism underlying orotic acid-mediated improvement in function is implicated. Nevertheless, orotic acid may be a therapeutic agent facilitating long-term recovery from global ischemia.
Animals↗
Platelet-derived growth factor induces fetal wound fibrosis.
The fetal response to cutaneous injury differs markedly from that of the adult, proceeding with only minimal inflammation, minimal fibroblast proliferation, and only essential collagen deposition. Although the sequence of events in adult wound healing is well defined and thought to be controlled in part by potent polypeptide cytokines, relatively sparse information exists regarding growth factor involvement in fetal wound repair. Thus, the authors sought to examine the effect of platelet-derived growth factor (PDGF), a putative adult wound healing regulator, on the cellular and extracellular matrix events at a fetal wound site. SILASTIC wound implants containing 0, 1.0, 5.0, or 10.0 ng of human PDGF were placed subcutaneously on the backs of 24-day-gestation fetal rabbits (full term, 31 days) and then harvested after either 1, 3, or 5 days in utero. The specimens underwent standard histological processing and were evaluated in a blinded fashion. Compared with controls, PDGF-treated implants had a marked increase in acute inflammation, fibroblast recruitment, and collagen and hyaluronic acid deposition; these differences appeared to be largely time- and PDGF dose-dependent. Thus, the fetal system is responsive to an adult wound healing mediator, and these data suggest that fetal repair proceeds in the absence of PDGF.
Animals↗
Parathyroid cysts: report of the sixth and youngest pediatric case.
A nonfunctioning parathyroid cyst occurred in an 8-year-old girl, the youngest patient reported to have this diagnosis. Most cysts are asymptomatic; a few are associated with signs and symptoms of hyperparathyroidism. In asymptomatic patients with a lateral neck cyst, aspiration of clear fluid with an elevated parathyroid hormone level is diagnostic of a parathyroid cyst. If this results in disappearance of the cyst, without recurrence, no further treatment is necessary. If the cyst recurs, aspiration may be repeated. However, persistence of the cyst despite aspiration or recurrence after the second aspiration should prompt surgical removal, with intraoperative identification of all parathyroid glands, because functioning parathyroid cysts are associated with a high risk of hyperplasia or adenoma.
Child↗