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Biomedical subjects

A DeVries

Publications and source records attributed to A DeVries.

13 recordsLinked to original sources

[The role of radiotherapy in the treatment of malignant meningiomas].

PURPOSE: Most malignant meningiomas will recur following surgical resection only. The role of irradiation and radiation dose levels is poorly defined. This study reviews a single institution experience using both, conventional and high doses > or = 60 Gy/CGE radiation regimen. PATIENTS AND METHODS: Between 1974 and 1995 16 patients with histologically proven malignant meningioma underwent radiation therapy (RT). Age at diagnosis ranged between 6 and 79 years (median: 49 years). Three patients reported previous irradiation to the head at least 14 years prior to diagnosis. Ten patients were treated for primary, and 6 patients for recurrent disease. Six patients underwent gross total and 10 patients subtotal resection (Table 1). RT was delivered using conventional, megavoltage photons or combined 160 MeV proton and photon irradiation. Except 1 patient, who died during RT, the radiation doses ranged between 40 and 70 Gy/CGE (= Cobalt Gray Equivalent) (median: 58 Gy/CGE, Table 2). RESULTS: With median observation time of 59 months (range: 10 to 155 months), actuarial local control rates at 5 and 8 years were 52% and 17%, respectively. Target doses > or = Gy/CGE resulted in significantly improved tumor control (100%) compared to < 60 Gy/CGE (17%) (p = 0.0006, Table 3 and Figure 1). Improved local control translated also in increased overall survival: 87% (> or = 60 Gy/CGE) versus 15% (< 60 Gy/CGE) at 5 years (p = 0.025, Figure 2). At time of analysis, 6/16 patients (38%) were alive. Two patients developed symptomatic brain damage at doses of 59.3 and 72 Gy/CGE. CONCLUSION: Conformal, radiation therapy with target doses > or = 60 Gy/CGE, in this study by use of combined proton and photon irradiation, can significantly improve chances of long-term local control and survival for patients diagnosed with these challenging tumors.

Adolescent

Proton radiation therapy for chordomas and chondrosarcomas of the skull base.

OBJECT: Local tumor control, patient survival, and treatment failure outcomes were analyzed to assess treatment efficacy in 58 patients in whom fractionated proton radiation therapy (RT) was administered for skull base chordomas and chondrosarcomas. METHODS: Between March 1992 and January 1998, a total of 58 patients who could be evaluated were treated for skull base tumors, 33 for chordoma and 25 for chondrosarcoma. Following various surgical procedures, residual tumor was detected in 91% of patients; 59% demonstrated brainstem involvement. Target dosages ranged from 64.8 and 79.2 (mean 70.7) Co Gy equivalent. The range of follow up was 7 to 75 months (mean 33 months). In 10 patients (17%) the treatment failed locally, resulting in local control rates of 92% (23 of 25 patients) for chondrosarcomas and 76% (25 of 33 patients) for chordomas. Tumor volume and brainstem involvement influenced control rates. All tumors with volumes of 25 ml or less remained locally controlled, compared with 56% of tumors larger than 25 ml (p = 0.02); 94% of patients without brainstem involvement did not experience recurrence; in patients with brainstem involvement (and dose reduction because of brainstem tolerance constraints) the authors achieved a tumor control rate of 53% (p = 0.04). Three patients died of their disease, and one died of intercurrent disease. Actuarial 5-year survival rates were 100% for patients with chondrosarcoma and 79% for patients with chordoma. Grade 3 and 4 late toxicities were observed in four patients (7%) and were symptomatic in three (5%). CONCLUSIONS: High-dose proton RT offers excellent chances of lasting tumor control and survival, with acceptable risks. In this series all small- and medium-sized tumors with no demonstrable brainstem involvement have been controlled; all such patients are alive. Surgical debulking enhanced delivery of full tumoricidal doses, but even patients with large tumors and disease abutting crucial normal structures benefited.

Actuarial Analysis

Comparison of chromosome telomere integrity in multiple tissues from subjects at different ages.

Telomere DNA, at the ends of each chromosome, is conserved in nature and required for chromosome replication and stability. Reduction in telomere length has been observed in several malignancies as well as in leukocytes from healthy persons with advancing age. There is a paucity of data regarding telomere length and the effects of in vivo aging in different tissues. These data could be helpful in interpreting telomere length and understanding the role of telomere integrity and telomerase activity in malignant cells. We report telomeric DNA integrity studies of blood and skin collected from eight Caucasians of both sexes representing each decade of life from the fetus to 72 years of age without exposure to chemotherapy or radiation. In addition, telomeric data from 15 other tissues from the fetus and 8 other tissues from the 72-year-old male were examined. No significant differences were found in the shortest telomere size, the average telomere size, or telomere size variation between blood and skin from subjects at different ages. The average telomere size was 11.7 +/- 2.2 kb for blood and 12.8 +/- 3.7 for skin in all subjects studied. The shortest telomere length was 5.4 +/- 1.9 kb for blood and 4.3 +/- 0.9 kb for skin. Significant differences (P < 0.001) were found in the overall length of the DNA hybridization signal representing the shortest telomere size and the length of the DNA peak migration hybridization signal representing variation in telomere size between the 20-week fetus and the 72-year-old male. The 72-year-old male showed the shortest telomeres and the most variation (heterogeneity) in telomere size for all tissues studied, but the greatest differences were observed in blood compared with other tissues (e.g., average telomere length was 12.2 kb in the fetus and 7.2 kb in the 72-year-old male). The size of the telomere was negatively correlated with age for all tissues studied.

Adolescent

Lectin intravital perfusion studies in tumor-bearing mice: micrometer-resolution, wide-area mapping of microvascular labeling, distinguishing efficiently and inefficiently perfused microregions in the tumor.

Intravital lectin perfusion was combined with computer-guided scanning digital microscopy to map the perfused elements of the vasculature in tumor-bearing mice. High-precision composite images (spatial precision 1.3 micron and optical resolution 1.5 micron) were generated to permit exact positioning, reconstruction, analysis, and mapping of entire tumor cross-sections (c. 1 cm in diameter). Collation of these mosaics with nuclear magnetic resonance maps in the same tumor plane identified sites of rapid contrast medium uptake as tumor blood vessels. Digitized imaging after intravital double labeling allowed polychromatic visualization of two different types of mismatched staining. First, simultaneous application of two lectins, each bearing a different fluorochrome, revealed organ-specific differential processing in the microvascular wall. Second, sequential application of two boluses of one lectin, bearing different fluorochromes successively, distinguished between double-labeled microvessels, representing efficiently perfused vascular segments, and single-labeled microvessels, with inefficient or intermittent perfusion. Intravital lectin perfusion images of blood vessels in the vital functional state thus highlighted biologically significant differences in vessel function and served as high-resolution adjuncts to MR imaging.

Adenocarcinoma

Do specialists order too many tests? The case of allergists and pediatric asthma.

BACKGROUND: Is the practice style of specialists overly reliant on diagnostic tests? Health maintenance organization managers and other clinicians have been critical of the high cost practice styles of specialists, but if the specialists' practice style ultimately results in similar or lower total costs because of better outcomes in the treatment of exceptional cases, then such practice styles are cost-effective and should be encouraged. Indeed, if this is the case, not employing a test-intensive practice style could be considered negligent under a legal criterion. OBJECTIVE: We attempted to determine whether the care of pediatric asthmatic patients by allergists is characterized by more testing, but by better, less costly outcomes than care by non-allergists. METHODS: We used administrative data on pediatric asthmatic cases from a large health care plan from 1992 to determine whether patients treated by allergists received more tests, cost more, and had fewer asthmatic management breakdowns than patients treated by non-allergists. We used regression analysis to hold constant aspects of the patient's case mix. RESULTS: Although allergists ordered significantly more tests than non-allergists, their overall treatment costs were similar. Patients treated by allergists had fewer management breakdowns. CONCLUSIONS: These results suggest that the allergists' test-intensive practice style is cost-effective.

Allergy and Immunology

Evidence for genetic heterogeneity of malignant hyperthermia susceptibility.

A locus for malignant hyperthermia susceptibility (MHS) has been localized on chromosome 19q12-13.2, while at the same time the gene encoding the skeletal muscle ryanodine receptor (RYR1) also has been mapped to this region and has been found to be tightly linked to MHS. RYR1 was consequently postulated as the candidate for the molecular defect causing MHS, and a point mutation in the gene has now been identified and is thought to be the cause of MH in at least some MHS patients. Here we report the results of a linkage study done with 19q12-13.2 markers, including the RYR1 cDNA, in two Bavarian families with MHS. In one of the families, three unambiguous recombination events between MHS and the RYR1 locus were found. In the second family only one informative meiosis was seen with RYR1. However, segregation analysis with markers for D19S75, D19S28, D19S47, CYP2A, BCL3, and APOC2 shows that the crossovers in the first family involve the entire haplotype defined by these markers flanking RYR1 and, furthermore, reveals multiple crossovers between these haplotypes and MHS in the second family. In these families, pairwise and multipoint lod scores below -2 exclude MHS from an interval spanning more than 26 cM and comprising the RYR1 and the previously described MHS locus. Our findings thus strongly suggest genetic heterogeneity of the MHS trait and prompt the search for another MHS locus.

Adult

Mucin biosynthesis. Enzymic properties of human-tracheal epithelial GDP-L-fucose:beta-D-galactoside alpha-(1----2)-L-fucosyltransferase.

The human-tracheal, epithelial alpha-(1----2)-L-fucosyltransferase that transfers L-fucose from GDP-L-fucose to an acceptor containing a beta-D-galactopyranosyl group at the nonreducing terminal was characterized. Optimal enzyme activity was obtained at pH 6.5. 20-30mM MnCl2 (or CaCl2), and 0.05% Triton X-100 or 0.5% Tween 20. Mg2+ and Ba2+ ions moderately enhanced the enzyme activity, whereas Fe2+, Co2+, Zn2+, and Cd2+ ions were inhibitory. The enzyme activity was inhibited by N-ethylmaleimide and nucleotides of guanine, inosine, xanthine, and uridine. However, ATP and dithiothreitol did not affect the enzyme activity. The apparent Michaelis constant for GDP-L-fucose, freezing point-depressing glycoproteins (expressed as Gal----GalNAc----Thr), and phenyl beta-D-galactopyranoside was 0.29, 5.70, and 25.4mM, respectively. Under alkali-borohydride conditions (0.05M NaOH-M NaBH4, 45 degrees, 20 h), an L-[14C]fucosyltrisaccharide was released from the product obtained by use of freezing point-depressing glycoprotein as the acceptor. The alpha-L anomeric configuration of the fucoside was determined by the release of L-[14C]fucose from the purified trisaccharide by Turbo cornutus alpha-L-fucosidase. The (1----2) linkage of the L-fucosyl group to the D-galactosyl residue was established by methylation technique (m.s.-g.l.c.). The present enzyme has properties similar to those of the human milk alpha-(1----2)-L-fucosyltransferase which is encoded by a secretor gene.

Cations, Divalent

Pharmacokinetic MRI for assessment of malignant glioma response to stereotactic radiotherapy: initial results.

The purpose of this study was to assess the value of dynamic, contrast-enhanced MRI in patients with malignant glioma (a) to predict before stereotactic radiotherapy local tumor control, (b) to investigate temporal changes in tumor microcirculation after stereotactic radiotherapy, and (c) to analyze whether malignant glioma response may be predicted earlier by alterations in the tissue pharmacokinetics rather than in terms of tumor volume. Ninety MRI studies were performed of 18 patients with malignant glioma before and 6, 18, 26, 52, and 72 weeks after the end of stereotactic radiotherapy. The signal time courses of the contrast-enhanced tumors were analyzed using a pharmacokinetic two-compartment model that calculates for the parameter A, reflecting the degree of MRI signal enhancement [no units] and the exchange rate constant k21 [min(-1)]. Before radiotherapy, the amplitude A was significantly (P < .05) lower in patients with subsequent local tumor control (n = 8; mean A = .34 +/- .15) compared to patients without subsequent local tumor control (n = 10; mean A = .94 +/- .71). In the local tumor control group, early after stereotactic radiotherapy (at 6-18 weeks), there was a significant (P < .05) time-dependent decrease in the parameter k21, whereas there was still no alteration in the tumor volume. A low amplitude A before radiotherapy, combined with an early drop of k21 after stereotactic radiotherapy, reliably characterized the group of patients with subsequent tumor volume decrease. Our preliminary results suggest that two contrast-enhanced dynamic MR studies, one before and one early after stereotactic radiotherapy, offer important information on local tumor control within the first 6 to 18 weeks after stereotactic radiotherapy. Moreover, this response may be evidenced before tumor volume changes and provides a therapeutic window to broaden treatment options and to improve treatment outcome.

Brain

Ketoconazole in the prevention of acute respiratory distress syndrome.

We conducted a critical review of the literature on ketoconazole in preventing acute respiratory distress syndrome (ARDS), a serious disorder associated with high mortality. Two double-blind, prospective, placebo-controlled, randomized trials compared ketoconazole with placebo for prophylaxis of ARDS. In one trial, compared with placebo, ketoconazole resulted in a reduced frequency of ARDS (6% vs 31%, p<0.01), lower plasma thromboxane B2 levels (33 vs 75 pg/ml, p<0.05), and shorter intensive care unit stay (7 vs 15.5 days, p<0.05). In the second trial the drug reduced the frequency of ARDS (15% vs 64%, p=0.002), lowered thromboxane B2 levels (83 vs 143 pg/ml), and reduced mortality (15% vs 39%, p=0.05) compared with placebo. Larger multicenter studies are warranted to validate the findings of these two trials.

Antifungal Agents