Diffuse nephrocalcinosis: hyperechoic sonographic appearance.
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Calcinosis↗
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Results for “Mack v. Mack”
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Treatment of ovarian cancer with a tropism modified oncolytic adenovirus.
Ad5-Delta 24RGD is an adenovirus that is selectively replication competent in cells defective in the Rb/p16 pathway, such as ovarian cancer cells. The fiber of Ad5-Delta 24RGD contains an integrin binding RGD-4C motif, allowing Coxsackie adenovirus receptor-independent infection of cancer cells. Oncolysis of cell lines was similar to that of a wild-type control, and replication in primary tumor material was shown using a novel three-dimensional spheroid model. Finally, an orthotopic murine model of peritoneally disseminated ovarian cancer was used to test i.p. administration to tumor-bearing animals. Injection of the agent resulted in eradication of i.p. disease, whereas control animals expired (P < 0.0001). These results suggest that Ad5-Delta 24RGD could be useful for treatment of ovarian cancer in humans.
Adenoviridae↗
Developing a Web site in primary care.
BACKGROUND AND OBJECTIVES: While content, navigability, and usability are essential qualities of effective Web sites, the health care literature contains limited discussion of these issues. This article describes how knowledge gained through focus groups, Web site searches, and individual interviews were used to develop and improve a health-related Web site. METHODS: We conducted 10 focus groups and searches of existing Web sites in preparation for developing a Web site about colorectal cancer (CRC) screening. We conducted 30 in-depth interviews to assess content, navigation, and usability of a new CRC Web site, using participants recruited from Michigan communities with a low incidence of CRC testing. Targeted participants were 50-70 years of age, had no prior experience with CRC testing, and had variable comfort levels with Internet use. RESULTS: Existing CRC screening Web sites uniformly use user-directed navigation and have little variation in content. Our study participants stimulated revisions in content, navigation, and usability. Revised content factors included comprehension, utility, and appeal. Navigation changes focused on logical transition between sections. Usability changes included user focus and clarity of graphics/ text. CONCLUSIONS: We found focus groups, Web site searches, and individual interviews useful in developing and testing content, navigation, and usability of a CRC screening Web site. These steps provide methodological procedures for developing and revising health-related Web sites.
Aged↗
Glycine protects hepatocytes from injury caused by anoxia, cold ischemia and mitochondrial inhibitors, but not injury caused by calcium ionophores or oxidative stress.
Isolated hepatocytes, suspended in an organ preservation solution, can be preserved at 4 degrees C for up to 6 days. After preservation, normothermic-normoxic incubation causes loss of hepatocyte viability. The addition of 3 mmol/L glycine to the rewarming medium prevents the loss of viability. In this study we investigated the cytoprotective effects of glycine under many conditions known to cause hepatocellular injury to understand the mechanism of cold-induced injury in the liver. Hepatocytes were suspended in modified Krebs-Henseleit buffer with or without 3 mmol/L glycine and exposed to agents or conditions known to induce cell death. Hepatocyte viability was assessed by measuring the percentage of lactate dehydrogenase leakage from the cells and the concentration of ATP during incubation at 37 degrees C under room air for up to 90 min. Mitochondrial inhibitors (potassium cyanide and carbonyl cyanide m-chlorophenylhydrazone); calcium ionophores (ionomycin and A23187); an oxidizing agent, tert-butyl hydroperoxide; and anoxia were all used to cause cell injury. Hepatocytes were also isolated from fasted rats and hypothermically preserved as another model of cell death. Other amino acids were also tested in the hypothermic preservation model to study the specificity of the amino acid requirement for prevention of lactate dehydrogenase leakage. Of the amino acids tested, only alanine (10 mmol/L) and the combination of alanine (3 mmol/L) and serine (3 mmol/L) were as effective as glycine in preventing lactate dehydrogenase release in the hypothermic preservation model.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acids↗
Comparison of cold and warm ischemic injury in hepatocytes from the rat liver.
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Alanine Transaminase↗
Trauma-induced alterations in macrophage function.
BACKGROUND: The juxtaposition of immune suppression and a hyperactive inflammatory response after injury represents a paradox in immune function. The aim of this study was to evaluate the delayed macrophage hypersecretion of inflammatory mediators in relation to functional macrophage defects. METHODS: BALB/c mice were randomized to control or trauma (femur fracture plus 40% blood volume hemorrhage) groups. One and 7 days after injury, splenic macrophages were isolated and assayed for antigen presentation and the production of inflammatory mediators tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, prostaglandin E2, H2O2, and nitric oxide. RESULTS: One day after injury, there were significantly diminished macrophage antigen presentation and decreased mean production of TNF-alpha, IL-6, and H2O2. In contrast, 7 days after injury, splenic macrophages produced significantly increased mean amounts of TNF-alpha, IL-6, prostaglandin E2, H2O2, and nitric oxide, with a persistent functional defect in antigen presentation. CONCLUSIONS: This phasic response to trauma suggests a persistent state of macrophage dysregulation that may help explain the paradox of immune suppression, manifested by functional defects predisposing patients to increased infections, in the setting of inflammatory mediator hypersecretion, predisposing patients to the systemic inflammatory response syndrome/multiple organ dysfunction syndrome.
Animals↗
Changes in pulmonary and systemic haemodynamics after the administration of various vasodilators in patients with pulmonary hypertension.
The authors investigated the influence of some vasodilatory drugs on pulmonary and systemic haemodynamic parameters in 69 patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (with the exception of two patients with diffuse pulmonary fibrosis and one patient with recurrent pulmonary thromboembolism). The investigated vasodilatory drugs were as follows: Dihydralazine Spofa--8 patients, Corinfar--10 patients, Ketanserin--13 patients, Nit-Ret 7 patients, Nitroglycerin Spofa--10 patients, Nitro-Mack--11 patients, Iso-Mack retard--10 patients. The haemodynamic parameters were measured before and at various time intervals after the administration of the vasodilatory agent (Dihydralazine 50 mg perorally--30th and 60th minute, Corinfar--20 mg sublingually--60th minute, and in 7 patients following a 6 months period of 30-60 mg Corinfar daily dose, Ketanserin--10 mg intravenously--10th, 20th and 40th minute, Nit-Ret--2.5 mg perorally--30th and 60th minute, Nitroglycerin Spofa--0.5 mg sublingually--10th and 30th minute, Nitro-Mack--1 mg intravenously--immediately following the end of a slow i. v. infusion for 20 minutes, Iso-Mack retard--20 mg perorally, 60th minute). The blood gases were measured at the same time intervals, too. The results in various groups were as follows: Dihydralazine administration was not followed by any significant change in PAP, CO, PVR, while a significant decrease in AOP and SVR was ascertained. A significant decrease of PaCO2 and no change in PaO2 were measured. Following Corinfar administration, no change in PAP, CO or PVR and a significant decrease of PaCO2 and no change in PaO2 were measured. Following Corinfar administration, no change in PAP, CO or PVR and a significant decrease in AOP were determined. No significant changes in blood gases were measured. Following a 6 month Corinfar treatment period in 7 subjects, no significant changes in pulmonary haemodynamics or blood gases values were found. No clinical benefit of this drug could be estimated. Ketanserin administration was not followed by any changes in pulmonary haemodynamics, whereas a significant decrease in AOP and SVR were found. The administration of Nit-Ret was followed by a significant decrease of CO, whereas no changes in PAP, AOP or PVR and SVR were found. No significant changes in the blood gas tenses values were measured. The administration of Nitroglycerin Spofa was followed by a significant decrease in RAP, PAP, AOP, RVEDP as well as in CO. No significant changes in blood gases were observed. The application of 1 mg Nitro-Mack intravenously was followed by a significant decrease in RAP, PAP, AOP and CO.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
A clinical evaluation of penicillin V in children with respiratory infections.
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Penicillin V↗
Genetic variability and linkage disequilibrium within the HLA-DP region: analysis of 15 different populations.
In order to understand the forces governing the evolution of the genetic diversity in the HLA-DP molecule, polymerase chain reaction (PCR)-based methods were used to characterize genetic variation at the DPA1 and DPB1 loci encoding this heterodimer on 2,807 chromosomes from 15 different populations including individuals of African, Asian, Amerindian, Indian and European origin. These ethnically diverse samples represent a variety of population substructures and include small, isolated populations as well as larger, presumably admixed populations. Ten DPA1 and 39 DPB1 alleles were identified and observed on 87 distinct DP haplotypes, 34 of which were found to be in significant positive linkage disequilibrium in at least one population. Some haplotypes were found in all ethnic groups while others were confined to a single ethnic group or population. Strong positive global linkage disequilibrium (Wn) between DPA1 and DPB1 was present in all 15 populations. The African populations displayed the lowest values of Wn whereas the Amerindian populations displayed near absolute disequilibrium. Analysis of the distribution of haplotypes using the normalized deviate of the Ewens-Watterson homozygosity statistic, F, suggests that DP haplotypes encoding the functional heterodimer are subject to much lower degrees of balancing selection than other loci within the HLA region. Finally, neighbor joining tree analyses demonstrate the power of haplotype diversity for inferring the relationships between the different populations.
Alleles↗
Glutathione S-transferases of female A/J mouse liver and forestomach and their differential induction by anti-carcinogenic organosulfides from garlic.
This study characterizes glutathione (GSH) S-transferase (GST) isoenzymes of the liver and forestomach of the female A/J mouse and compares their specificities in catalyzing the conjugation of GSH with 7beta,8alpha-dihydroxy-9alpha,10alpha-oxy-7,8,9, 10-tetrahydrobenzo[a] pyrene (anti-BPDE), the ultimate carcinogenic metabolite of benzo[a]pyrene (BP). The GST activity in female A/J mouse liver was expressed by a minimum of seven isoenzymes which arose from different homo- or heterodimeric combinations of at least two alpha class (designated as alpha1 and alpha4), four micro class (micro1 to micro4), and one pi class GST subunit. The GST isoenzyme composition of A/J mouse forestomach appeared to be different from that of the liver. For example, while GST isoenzymes containing micro3 and micro4 type subunits were selectively expressed in the liver, an alpha class heterodimeric GST isoenzyme (containing alpha2 and alpha3 subunits) was expressed in the forestomach but could not be detected in the liver. The (+)-anti-BPDE appeared to be a better substrate than the (-)-enantiomer for all GSTs, except for isoenzymes containing the alpha4 type GST subunit. The murine pi class GST isoenzyme displayed relativey higher specific activity toward (+)-anti-BPDE compared to other GSTs. The specific activities of mouse GSTs toward (+)-anti-BPDE were in the order of pi > micro > alpha. These results suggest that the pi class GST isoenzyme may play an important role in providing protection against BP-induced cancer. Therefore, it seems logical to postulate that the ability of a chemoprotector to increase the expression of GST pi may be an important determinant of its effectiveness against BP-induced cancer. To test the validity of this contention, we have determined the effects on hepatic and forestomach GST isoenzyme/subunit expression of three naturally occurring organosulfides (OSCs) from garlic, which significantly differ in their effectiveness against BP-induced forestomach cancer. Treatment of mice with diallyl sulfide (DAS) and diallyl trisulfide (DATS), which are potent inhibitors of BP-induced fore- stomach cancer in mice, resulted in a significant increase in hepatic and forestomach GST activity toward anti-BPDE. On the contrary, this activity was not increased in either organ by dipropyl sulfide (DPS), which is ineffective against BP-induced forestomach cancer. The chemopreventive efficacy of these OSCs correlated with their ability to increase the expression of GST pi. For example, DAS treatment resulted in approximate increases of 1.7- and 2.2-fold in hepatic and forestomach GST pi expression, respectively, over the control. Treatment of mice with DATS, which is a relatively more potent inhibitor of BP-induced forestomach cancer than DAS, resulted in about 3.8- and 3.2-fold increases, respectively, in hepatic and forestomach GST pi expression over the control. On the contrary, the expression of hepatic and forestomach GST pi was increased only marginally (10-20%) upon DPS administration. In conclusion, the results of the present study suggest that induction of GST pi can be used as a bioassay for screening potential inhibitors of BP-induced cancer.
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
Activation of K+ and Cl- channels by Ca2+ and cyclic AMP in dissociated kidney epithelial (MDCK) cells.
In dissociated MDCK cells, activators of the cyclic AMP system cause depolarization detectable by changes in fluorescence of the membrane potential sensitive dye bisoxonol. Addition of forskolin (60 microM), vasopressin (2 microM), 8-bromo-cyclic AMP (0.5 mM) or 1-epinephrine (10 microM) depolarized the cells substantially in low Cl- (5 mM) but had little effect in high Cl- (140 mM) solution. These results are consistent with cyclic AMP activation of Cl- channels. The Ca2+-ionophore ionomycin (1 microM) produced a rapid hyperpolarization in low and high Cl- solutions, consistent with K+ channel opening. Using a clonal subline, MDCK-14, the magnitude of the ionomycin hyperpolarization was roughly proportional to the concomitant rise in [Ca2+]i as measured with the intracellular Ca2+ probe indo-I. Both l-epinephrine and isoproterenol appeared to activate the Cl- channels. However only l-epinephrine produced a [Ca2+]i rise and a transient hyperpolarization (due to K+ channel opening), which preceded the depolarization due to Cl- channel opening. The l-epinephrine-induced [Ca2+]i response of the heterogeneous MDCK cell population but not of the clonal subline MDCK-14 was inhibited by removal of extracellular Ca2+. In the latter only the slow secondary phase of the [Ca2+]i rise was affected by Ca2+ removal. It is concluded that l-epinephrine activates K+ and Cl- channels in a sequential manner in MDCK cells by Ca2+ and cAMP signals, presumably via alpha- and beta-adrenergic receptors located on the same cell.
Animals↗
Enhancement of conductive anion permeability in cultured cells by cetiedil.
Cetiedil, a drug that is reported to block K+-channels, substantially increases the conductive C1- permeability of Chinese hamster ovary (CHO) cells. The permeability was monitored by volume changes in cells treated with gramicidin to increase the cation permeability. Under this circumstance, increases in Cl- conductances result in volume changes detectable by electronic sizing, with the direction determined by the gradients of the permeating ions. In NaCl or KCl media, swelling occurs, but in N-methylglucamine chloride, shrinking. The increases in Cl- conductance could also be measured as an increased 36Cl- flux or by changes in membrane potential (measured by fluorescence of a potential-sensitive dye) toward the Cl- equilibrium potential. The effect of cetiedil was concentration dependent, with maximal effect at 50 microM. The anion specificity for the conductance was NO3- greater than Cl- = Br- much greater than SO4-2 or isethionate. A number of other drugs that influence transport activities had no effect on Cl- conductance. The cetiedil effect on Cl- conductance was observed in one other cell line, but was absent in several other cell types. The cetiedil-induced Cl- conductance in CHO cells appears to involve a different pathway than that induced by exposure to hypotonic medium.
Animals↗
Photogrammetric accuracy measurements of head holder systems used for fractionated radiotherapy.
PURPOSE: We describe how stereo photogrammetry can be used to determine immobilization and repositioning accuracies of head holder systems used for fractionated radiotherapy of intracranial lesions. METHODS AND MATERIALS: The apparatus consists of two video cameras controlled by a personal computer and a bite block based landmark system. Position and spatial orientation of the landmarks are monitored by the cameras and processed for the real-time calculation of a target point's actual position relative to its initializing position. The target's position is assumed to be invariant with respect to the landmark system. We performed two series of 30 correlated head motion measurements on two test persons. One of the series was done with a thermoplastic device, the other one with a cast device developed for stereotactic treatment at the German Cancer Research Center. Immobilization and repositioning accuracies were determined with respect to a target point situated near the base of the skull. The repositioning accuracies were described in terms of the distributions of the mean displacements of the single motion measurements. RESULTS: Movements of the target in the order of 0.05 mm caused by breathing could be detected with a maximum resolution in time of 12 ms. The data derived from the investigation of the two test persons indicated similar immobilization accuracies for the two devices, but the repositioning errors were larger for the thermoplastic device than for the cast device. Apart from this, we found that for the thermoplastic mask the lateral repositioning error depended on the order in which the mask was closed. CONCLUSION: The photogrammetric apparatus is a versatile tool for accuracy measurements of head holder devices used for fractionated radiotherapy.
Head and Neck Neoplasms↗
The role of intraoperative parathyroid hormone testing in patients with tertiary hyperparathyroidism after renal transplantation.
BACKGROUND: Intraoperative parathyroid hormone (PTH) testing has been shown to accurately define adequacy of parathyroid resection in patients with primary hyperparathyroidism (HPT) and alters the operative management in 10% to 15% of cases. However, the benefit of this technique in patients with tertiary HPT after renal transplantation undergoing parathyroidectomy is unclear. METHODS: Intraoperative PTH was measured in 32 consecutive patients undergoing parathyroidectomy for tertiary HPT after renal transplantation between March 2001 and November 2004 by using the Elecsys assay at baseline and, subsequently, 5, 10, and 15 minutes after curative resection. The outcomes of these patients were evaluated. RESULTS: All patients were cured after surgery. Of the 32 patients, 29 were found to have parathyroid hyperplasia, while 1 had a single adenoma and 2 had double adenomas. The average drop in intraoperative PTH levels after curative resection was 69 +/- 3.5% at 5 min., 77 +/- 2.3% at 10 minutes, and 83 +/- 3.4% at 15 minutes. PTH testing changed the intraoperative management in 5 (16%) patients. One patient with a single adenoma and 2 patients with double adenomas had a >50% drop at 10 minutes. after excision; therefore, the operation was terminated without further resection. Two patients did not have a >50% drop at 10 minutes after 3.5 gland resection. These patients were explored further, and additional supernumerary parathyroid glands were identified and resected. After resection of these additional glands, the PTH fell by >50%, indicating cure. CONCLUSIONS: In patients undergoing parathyroidectomy for tertiary HPT after renal transplantation, a decrease in intraoperative PTH levels >50% at 10 minutes after completion of the operation indicated adequate resection. Furthermore, intraoperative PTH testing altered the operative management in 16% of patients. Therefore, similar to its role in patients with primary HPT, intraoperative PTH testing appears to play an equally important role in the management of patients with tertiary HPT undergoing parathyroidectomy.
Female↗
Frequency of positive biopsies after visual disappearance of superficial bladder cancer marker lesions.
INTRODUCTION AND OBJECTIVES: In phase II trials in superficial bladder cancer, marker lesions have been used to test the ablative activity of intravesical chemo- or immunotherapy. These studies provide important knowledge about drug activity and toxicity without exposing hundreds of patients in phase III trials to drugs which ultimately may not be successful in preventing tumour recurrence or progression. After treatment a deep biopsy was necessary at the site of the marker lesion even in the absence of any visual tumour. The question is if this biopsy, in the absence of any visual tumour, should be done. MATERIAL AND METHODS: The ablative effect of MMC, epirubicin, and quarter dose BCG instillations was evaluated in three different studies on a papillary marker lesion. Patients with multiple, primary or recurrent superficial bladder tumours were included. All visible Ta-T1 lesions were resected except for one marker lesion not exceeding 1 cm. TIS was excluded. In the last study, patients with T1 G3 tumours or multiple tumours >10 were also excluded. If the marker lesion disappeared completely, a deep biopsy was performed at the scar in order to prove histological disappearance of the tumour. RESULTS: 185 patients were evaluated. No visual tumours were seen in 110 patients and a TUR was performed in 101 of them. It revealed only 3 Ta lesions. In the 9 others no biopsy was performed but follow-up cystoscopy revealed no lesions. CONCLUSIONS: In the absence of any visual tumors, TUR and deep biopsy at the site of the scar of the marker lesion only rarely revealed (3 out of 110) the histological presence of a tumour. Therefore, this biopsy can be omitted in new marker lesion protocols in patient with Ta-T1, G1 G2 papillary superficial bladder tumours at intermediate risk for recurrence and low risk for progression.
Administration, Intravesical↗
A synthetic tumor necrosis factor-alpha agonist peptide enhances human polymorphonuclear leukocyte-mediated killing of Plasmodium falciparum in vitro and suppresses Plasmodium chabaudi infection in mice.
A peptide corresponding to residues 70-80 of the TNF-alpha polypeptide was synthesized and shown to enhance human PMN-mediated killing of Plasmodium falciparum in vitro and reduced the Plasmodium chabaudi parasitemia in mice. Studies of the mechanism of action showed that the peptide, TNF(70-80), stimulated and primed PMN for an increased respiratory burst and release of granule constituents in response to a second agonist. The PMN-stimulatory activity of the peptide was inhibited by mAbs against the p55 and p75 TNF receptors and a TNF-neutralizing mAb. Analysis of PMN receptor expression showed that CR3 (CD18/CD11b) and Fc gamma RIII were upregulated by TNF(70-80), which was consistent with the peptide's ability to enhance parasite killing by PMN. The peptide, unlike TNF, did not increase the expression of adhesion molecules on endothelial cells and failed to promote binding of P. falciparum-infected erythrocytes to endothelial cells. TNF(70-80) also inhibited the TNF-induced increase in adhesion of P. falciparum-infected erythrocytes to endothelial cells. The results demonstrate that the host-protective effects of TNF can be retained while toxic effects are eliminated using a selected, characterized subunit of the cytokine.
Animals↗
Single-dose concentrations of tinidazole in gingival crevicular fluid, serum, and gingival tissue in adults with periodontitis.
Previous studies have shown that metronidazole is effective in the treatment of subgingival microflora associated with destructive periodontitis. The aim of this study was to determine whether tinidazole, a close analogue of metronidazole, would reach sufficient concentrations in serum, gingival crevicular fluid, and gingival tissue, to inhibit putative periodontopathic bacteria. Ten adult patients with moderate to advanced periodontitis took a single 2-g dose of tinidazole orally. Samples were assayed by high-performance liquid chromatography. The concentrations of tinidazole in serum and GCF were in a similar range (3.2-46.5 micrograms/mL). Tinidazole was not detected in the GCF in three of the patients. The drug was found in gingival tissue obtained at two h (0.17 +/- 0.14 micrograms/mg) and six h (0.15 +/- 0.18 micrograms/mg) after oral administration. The mean concentration of tinidazole in serum at 24 h (13 +/- 3.0 micrograms/mL) is greater than the minimum inhibitory concentration for anaerobic bacteria as reported by others. The present data suggest that a single 2-g oral dose of tinidazole may lead to the presence of potentially bactericidal levels of tinidazole for up to 24 h in the periodontal pockets of some patients with periodontitis.
Administration, Oral↗
Treatment with nephrectomy only for small, stage I/favorable histology Wilms' tumor: a report from the National Wilms' Tumor Study Group.
PURPOSE: Children younger than 24 months with small (< 550 g), favorable histology (FH) Wilms tumors (WTs) were shown in a pilot study to have an excellent prognosis when treated with nephrectomy only. PATIENTS AND METHODS: A study of nephrectomy only for the treatment of selected children with FH WT was undertaken. Stringent stopping rules were designed to insure closure of the study if the true 2-year relapse-free survival rate was 90% or lower. RESULTS: Seventy-five previously untreated children younger than 24 months with stage I/FH WTs for which the surgical specimen weighed less than 550 g were treated with nephrectomy only. Three patients developed metachronous, contralateral WT 1.1, 1.4, and 2.3 years after nephrectomy, and eight patients relapsed 0.3 to 1.05 years after diagnosis (median, 0.4 years; mean, 0.51 years). The sites of relapse were lung (n = 5) and operative bed (n = 3). The 2-year disease-free (relapse and metachronous contralateral WT) survival rate was 86.5%. The 2-year survival rate is 100% with a median follow-up of 2.84 years. The 2-year disease-free survival rate (excluding metachronous contralateral WT) was 89.2%, and the 2-year cumulative risk of metachronous contralateral WT was 3.1%. CONCLUSION: Children younger than 24 months treated with nephrectomy only for a stage I/FH WT that weighed less than 550 g had a risk of relapse, including the development of metachronous contralateral WT, of 13.5% 2 years after diagnosis. All patients who experienced relapse on this trial are alive at this time. This approach will be re-evaluated in a clinical trial using a less conservative stopping rule.
Disease-Free Survival↗