Search PubMed⌕ Search

Biomedical subjects

A Wu

Publications and source records attributed to A Wu.

At least 145 records · Page 8Linked to original sources

Evaluation of radiosurgery techniques with cumulative dose volume histograms in linac-based stereotactic external beam irradiation.

Radiosurgery at UCSF is performed with a 6-MV linear accelerator with tertiary collimation for improved small field definition. The dose delivery to the target relative to normal tissue is influenced by the number of arcs, the arc geometry, field size, and beam energy. The impact of arc number, arc geometry, and field size on the dose distribution from 6-MV X rays in a 16 cm spherical phantom has been evaluated through the use of cumulative dose volume histograms. Dose volume histograms were calculated for a) 1-5 and 10 arcs, and b) collimator sizes of 1.25, 2.0, and 3.0 cm. Differences between techniques were found at the 5-10% level for field sizes from 1.25 to 2.0 cm. It was shown that the finite dimension of the sphere and, by extension, head diminishes the differences between techniques for the larger field sizes. The effect of treating with two isocenters is also analyzed and an approach for improving the dose distribution is presented.

Brain Diseases↗

The valuation of states of ill-health: the impact of age and disability.

The effects of age and disability on valuations of health states used in deriving QALYs have not been examined. We compared the valuations of seven states of immobility and pain given by 88 subjects aged 20-89 years, and of various degrees of disability. They were asked to score each state, their present health and death, on a range from 'best' to 'worst' health. Only two states of health (no disability but moderate pain, and slight disability and moderate pain) were valued differently by older subjects. Disabled subjects tended to rate most ill-health states more adversely, and to rate death as substantially better than more severe states of ill-health. The development of explicit valuations of survival should take into account differences caused by disability, and examine other dimensions of illness experience.

Adult↗

Rapid Enrichment of CHAPS-Solubilized UDP-Glucose: (1,3)-beta-Glucan (Callose) Synthase from Beta vulgaris L. by Product Entrapment : Entrapment Mechanisms and Polypeptide Characterization.

Rapid enrichment of CHAPS-solubilized UDP-glucose:(1,3)-beta-glucan (callose) synthase from storage tissue of red beet (Beta vulgaris L.) is obtained when the preparation is incubated with an enzyme assay mixture, then centrifuged and the enzyme released from the callose pellet with a buffer containing EDTA and CHAPS (20-fold purification relative to microsomes). When centrifuged at high speed (80,000g), the enzyme can also be pelleted in the absence of substrate (UDP-Glc) or synthesis of callose, due to nonspecific aggregation of proteins caused by excess cations and insufficient detergent in the assay buffer. True time-dependent and substrate-dependent product-entrapment of callose synthase is obtained by low-speed centrifugation (7,000-11,000g) of enzyme incubated in reaction mixtures containing low levels of cations (0.5 millimolar Mg(2+), 1 millimolar Ca(2+)) and sufficient detergent (0.02% digitonin, 0.12% CHAPS), together with cellobiose, buffer, and UDP-Glc. Entrapment conditions, therefore, are a compromise between preventing nonspecific precipitation of proteins and permitting sufficient enzyme activity for callose synthesis. Further enrichment of the enzyme released from the callose pellet was not obtained by rate-zonal glycerol gradient centrifugation, although its sedimentation rate was greatly enhanced by inclusion of divalent cations in the gradient. Preparations were markedly cleaner when product-entrapment was conducted on enzyme solubilized from plasma membranes isolated by aqueous two-phase partitioning rather than by gradient centrifugation. Product-entrapped preparations consistently contained polypeptides or groups of closely-migrating polypeptides at molecular masses of 92, 83, 70, 57, 43, 35, 31/29, and 27 kilodaltons. This polypeptide profile is in accordance with the findings of other callose synthase enrichment studies using a variety of tissue sources, and is consistent with the existence of a multi-subunit enzyme complex.

Journal Article↗

Effect of fixation on the amplification of nucleic acids from paraffin-embedded material by the polymerase chain reaction.

Amplification of nucleic acids from paraffin-embedded material by the polymerase chain reaction (PCR) is increasingly being used to detect viral genomes and oncogene mutations. To determine the effect of fixation on the preservation of the nucleic acids, we fixed two randomly chosen fresh pathology specimens in formalin, B-5, Bouin's, Zenker's, ethanol, and Omnifix for 6, 24, 48, 72, and 168 hr (1 week), and then embedded the tissue in paraffin. Oligonucleotide primers specific for the cytoplasmic-beta-actin gene were chosen to span an intron such that amplification yielded a product of 250 BP for DNA and 154 BP for RNA. A single 6-microns section was cut from each paraffin block, deparaffinized, and then subjected to 30 rounds of amplification for either DNA or RNA. On amplifying DNA, consistent product was seen in the ethanol and Omnifix specimens up to 72 hr of fixation time, whereas variable product was seen with formalin or Zenker's fixation; all specimens fixed in Bouin's or B-5 were negative. On amplifying RNA, a product could be detected even after 1 week of fixation in ethanol or Omnifix, and after 48 hr in the formalin-fixed tissue. The Zenker's-fixed tissues gave variable results, and the Bouin's and B-5 tissues gave consistent results only after 6 hr of fixation. We therefore conclude that choice of fixative and fixation time are critical factors influencing the outcome of PCR amplification of nucleic acids from paraffin-embedded material.

Base Sequence↗

Anti-CD8 abrogates effect of anti-CD4-mediated islet allograft survival in rat model.

We studied the effects of anti-CD4 treatment of diabetic ACI rats on the induction of tolerance to allogeneic (Lewis) islet allografts. When given as a 4-day treatment regimen, OX38, a mouse anti-rat CD4 antibody, caused depletion of greater than 80% of CD4+ cells from the peripheral blood of treated rats. After induction of diabetes (a single high-dose bolus of streptozocin) and 3 days after the initiation of anti-CD4 immunotherapy, recipient ACI rats were transplanted with fully allogeneic (Lewis) islets of Langerhans via the portal circulation. These transplanted islets were capable of returning the anti-CD4-treated ACI recipients to normoglycemia, which was maintained indefinitely in the absence of further immunosuppression. In contrast, treatment of recipient rats with OX8, an anti-CD8 monoclonal antibody (MoAb), induced only a slight prolongation of graft survival (less than or equal to 30 days). Further characterization of the cellular requirements for the induction of long-term transplantation survival revealed that successful pretransplantation anti-CD4 therapy could be ablated by the coincident treatment of recipient rats with depleting levels of anti-CD8 MoAb. These data point to the necessity of a regulator CD8+ cell in the induction of anti-CD4-mediated transplantation survival in this rat model of islet transplantation.

Animals↗

Predicted dose-volume isoeffect curves for stereotactic radiosurgery with the 60Co gamma unit.

Mathematical models were developed to predict tolerance of brain tissue to stereotactic radiosurgery. The use of these formulas for predicting symptomatic brain necrosis from stereotactic radiosurgery with the 60Co gamma unit is discussed. Predicted dose-response curves for different collimator sizes were calculated. Dose-volume isoeffect curves for a 3% risk of brain necrosis from a single fraction radiosurgery were then derived. Dose-volume isoeffect curves for combinations of fractionated whole brain irradiation with radiosurgery boosts were also calculated. The predicted dose-volume isoeffect curves provide useful tolerance guidelines for the practice of stereotactic radiosurgery.

Brain↗

The association between cervical carcinoma and human papilloma virus (HPV) in Xiangyuan County.

A mass survey was conducted to investigate the association between cervical carcinoma and human papilloma virus (HPV) infection in a high-risk area, Xiangyuan County, Shanxi Province. Fifty-four cases of cervical cancer in situ (CIS), including severe dysplasia (CIN III), 14 cases of invasive cervical carcinoma, 28 cases of mild cervical dysplasia (CIN I), and 13 cases of moderate cervical dysplasia (CIN II) were identified among 6710 women examined. One hundred and sixty-nine punch biopsies from abnormal cervix and genital tract were examined for the presence of HPV 6B/11, 16 and 18 DNA sequences by dot blot hybridization: The positive rates of HPV infection in cervicitis, CIN I, II, III, CIS and invasive cervical carcinoma specimens were 35.06% (27/77), 25% (2/8), 33.33% (2/6), 40% (2/5), 70.58% (24/34) and 40% (4/10), respectively. Among these groups, there was no regular distribution of HPV types except for HPV 16, the positive rate of which was increased from 25% in CIN I to 46.15% in CIS: HPV 16 was also the only type seen in the invasive cervical cancer group. Distribution analysis of HPV types in HPV-positive cervical cancer tissues uncovered an HPV 16 positive rate of 59.4%; 3.7 and 2.4 times higher than those of HPV 6B/11 and HPV 18, respectively. These data confirm the close association between cervical cancer and HPV 16 infection.

Adult↗

Complete functional recovery after 24-hour heart preservation with University of Wisconsin solution and modified reperfusion.

Successful long-term myocardial preservation is dependent on optimizing conditions during arrest, storage, and reperfusion. Neonatal piglet hearts were arrested and stored in University of Wisconsin solution (UW) at 4 degrees C for 24 hours and reperfused on a blood-perfused, adult animal-supported isolated circuit. Results were compared with nonischemic continuously perfused control hearts (group 1, n = 5). The initial 10 minutes of reperfusion in groups 2-4 was modified by aspartate/glutamate-enriched leukocyte-depleted blood cardioplegia (group 2, n = 7), leukocyte depletion alone (group 3, n = 9), and aspartate/glutamate-enriched blood cardioplegia alone (group 4, n = 6). After 10 minutes, perfusion was continued with unmodified whole blood. In group 5 (n = 9), unmodified whole blood was used for initial reperfusion as well as subsequent perfusion. The stroke work index was determined 60 minutes after reperfusion. Biopsies for high-energy phosphates, myocardial water content, and electron microscopy were obtained after functional assessment. The stroke work index at left ventricular end-diastolic pressure of 9 mm Hg did not differ between groups 1 and 2 (19.0 +/- 1.4 x 10(3) and 19.0 +/- 1.5 x 10(3) [mean +/- SEM] erg/g, respectively). These were both different from group 5 (13.3 +/- 0.8 x 10(3) erg/g, p less than 0.05). Group 3 showed improved function (15.7 +/- 0.7 x 10(3) erg/g), but this did not reach statistical significance when compared with group 5. No difference was found between groups 4 and 5. Myocardial water content, high-energy phosphate levels, and ultrastructure were similar in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Evaluation of second-look laparotomy for ovarian cancer: second-look vs. serum CA125.

Thirty patients with ovarian cancers underwent second-look operations in our hospital between 1981 and 1989, and the results were compared with serum CA125 values. The over-all positive rate determined by second-look laparotomy in the present series was 56.7% (17/30)-40% as gross and 17% an microscopic tumors. The result of the second-look was related to the staging and size of the residual tumor after the previous operation: 1/3 of stage I and II lesions and 16/27 of stage III and recurrent lesions were positive on second-look. The positive rates of those patients who were free from residual tumor and those with residual tumors less than or equal to 2 cm or greater than 2 cm were 28.6% (2/7), 60% (9/15) and 75% (6/8), respectively. Among the 23 patients assayed as to serum CA125 level before the second-look, 18 (78%) were within normal limits (less than 65 U/ml), including 12 patients (66.6%) who were second-look positive and 6 who were negative. Five patients with microscopic tumors and 3 patients with gross tumors less than or equal to 2 cm all had normal CA125 levels before the second-look. Among the 5 of 9 patients with gross tumors greater than 2 cm who had elevated CA125 levels, not one was found to be negative on second-look. This may imply that the elevated CA125 levels indicate recurrence, though a normal CA125 assay certainly does not preclude recurrence.

Adult↗

Environmental determinants of lung cancer in Shenyang, China.

To investigate determinants of the high rates of lung cancer in Shenyang, an industrial city in north-eastern China, a case-control study was conducted. Interviews with 1249 lung cancer patients and 1345 population-based controls revealed that cigarette smoking was the main cause of lung cancer. Smoking accounted for 55% of the lung tumours in men and 37% in women. In addition, air pollution from coal-burning heating and cooking devices was significantly linked to lung cancer, with risks rising in proportion to duration of exposure to indoor pollutants. Measurement of benzo[a]pyrene revealed average wintertime levels in air that were nearly 60 times the recommended upper limit for US cities, with even higher concentrations indoors in traditional single-storey homes using coal-burning kang (stoves). Occupational factors were also involved, the risk being elevated by three fold among smelter workers. Soil levels of arsenic and other metals rose with increasing proximity to the Shenyang copper smelter, and elevated risks of lung cancer were found among men, but not women, living within 1 km of its central stacks. Prior nonmalignant lung disease was common and was reported more often among the lung cancer patients than among controls. The findings suggest that cigarette smoking and environmental pollutants combine to account for most of the excess risk of lung cancer in this population.

Adult↗

Shielding requirements on-site loading and acceptance testing on the Leksell gamma knife.

On August 14, 1987, the first stereotactic radiosurgical procedure using the gamma knife was performed in North America. Located in a self-contained radiosurgical suite in the basement of Presbyterian-University Hospital in Pittsburgh, Pennsylvania. This device uses 201 highly focused beams 60Co for the single-treatment closed-skull irradiation of brain lesions localized by stereotactic techniques (radiosurgery). One hundred and fifty-two patients with intracranial arteriovenous malformations or brain tumors were treated in the first year of operation. The Presbyterian University Hospital of Pittsburgh gamma knife is the first such unit in which the 60Co sources were loaded on-site. This effort required us to solve some difficult and unusual problems encountered during site preparation, delivery, and loading of the unit in a busy hospital setting. The solutions developed enabled installation and use of the gamma knife with minimal disruption of hospital activities while maintaining acceptable levels of exposure to radiation. Environmental surveys performed during the loading of the 201 radioactive sources (total, 219 TBq) confirmed that on-site loading is possible and practical. Our experience in the design, construction, and implementation of the first North American gamma knife supports the practicality and safety of on-site loading and may be of value in the planning and development of future gamma knife installations.

Brain Neoplasms↗

Clinical use of a wing field with transmission block for the treatment of the pelvis including the inguinal node.

Treatment planning of photon and electron beams to include the pelvis and the groin poses a technical difficulty of positioning beams, and a dosimetric problem of abutting fields at the groin. We have analyzed a simpler AP/PA method using a central transmission block. The posterior portal is smaller and opposes only the pelvic portion of the anterior portal under the transmission block, while the anterior extended portion (hence the wing) is unattenuated to treat the inguinal region. By calculating the attenuation thickness according to the patient's separation and the beam quality, the dose distribution is tailored to yield the proper dose to the pelvic mid-plane and the inguinal nodes while minimizing the dose to the femora. Measured dose distribution (6MV) using film dosimetry in a tissue-equivalent phantom indicates that a 30% hot spot is created by the posterior portal diverging into the wings of the anterior field. Therefore, the pelvic attenuator is tapered at its lateral edges, thereby significantly reduced the dose inhomogeneity (5%) at the groin. Clinical methods are outlined for the verification of the patient portal films against possible mismatch in beam divergence.

Groin↗

Treatment planning for gamma knife radiosurgery with multiple isocenters.

Many arteriovenous malformations and tumors suitable for radiosurgical treatment have non-spherical or irregular shapes. Forty-eight percent of the first 156 patients treated with the gamma unit at the University of Pittsburgh required treatment with two or more isocenters to optimize dose distributions. Dose distributions for combining gamma knife treatments to two or more isocenters were systematically investigated. High speed computerized dosimetry was performed using specially developed software and dose distributions were confirmed with film densitometry. We have developed guidelines for treatment to two or more isocenters which help reduce treatment planning time, and facilitate selection of treatment doses and optimum dose distributions. These guidelines include maintaining an account of the distances between all isocenters, using a catalogue of sample two-isocenter isodose plans, comparing dose volume histograms, and calculating complication probabilities using the integrated logistic formula.

Cobalt Radioisotopes↗

Physics of gamma knife approach on convergent beams in stereotactic radiosurgery.

The Presbyterian-University Hospital of Pittsburgh installed the first clinically designated Leksell gamma knife in the U.S. in August 1987. Gamma knife radiosurgery involves stereotactic target localization with the Leksell frame and subsequent closed-skull single-treatment session irradiation of a lesion with multiple highly focused gamma ray beams produced from 60Co sources. The hemispherical array of sources, the large number of small-diameter beams, and the steep dose gradients surrounding a targeted lesion make physical characterization of the radiation field complex. This paper describes the physical features and the operation of the gamma knife as well as the calibration procedures of the very small, well-collimated beams. The results of studies using in-phantom ion chamber, diode, film, and lithium fluoride thermoluminescent dosimetry were all in close agreement. Both single-beam and multiple-beam dose profiles were measured and reported for the interchangeable helmets, which have 4-, 8-, 14-, and 18-mm-diameter collimators. We also describe the dose calculation and treatment planning algorithm in the treatment planning system. Measurements of the accuracy of mechanical and radiation alignment are also performed and discussed.

Brain Diseases↗

Treatment volume shaping with selective beam blocking using the Leksell gamma unit.

The Leksell gamma unit at the University of Pittsburgh uses 201 highly focused 60Co beams arranged in a hemispherical array. Selective beam blocking can be used to modify the treatment volume into ellipsoid shapes oriented in different directions to match better the shape of the target volume. Dose distributions for different blocking patterns were calculated using specially developed computerized 3-D treatment planning software. The changes in dose distribution with different blocking patterns predicted by computer were verified by film densitometry. Techniques for using selective beam blocking to match more closely the treatment volume to the intended target volume have the potential of reducing the likelihood of complications for radiosurgery with the Leksell gamma unit and need to be further developed.

Brain Neoplasms↗

In vivo biological effects of stereotactic radiosurgery: a primate model.

Single-fraction, closed skull, small-volume irradiation (radiosurgery) of intact intracranial structures requires accurate knowledge of radiation tolerance. We have developed a baboon model to assess the in vivo destructive radiobiological effects of stereotactic radiosurgery. Three baboons received a single-fraction, 150-Gy lesion of the caudate nucleus, the thalamus, or the pons using the 8-mm diameter collimator of the gamma unit. Serial standard neurodiagnostic tests (neurological examination, computed tomographic scan, magnetic resonance imaging, stable xenon-enhanced computed tomographic scan of cerebral blood flow, somatosensory and brain stem evoked potentials, and myelin basic protein levels of cerebrospinal fluid) were compared with preoperative studies. Magnetic resonance imaging revealed the development of a lesion at the target site between 45 and 60 days after irradiation. Deterioration of the brain stem evoked potentials preceded imaging changes when the lesion encroached on auditory pathways. Myelin basic protein levels increased subsequent to imaging changes. Postmortem neuropathological examination confirmed a well-demarcated radionecrosis of the target volume. The baboon model appears to be an excellent method to study the in vivo biological effects of radiosurgery.

Animals↗