Biomedical subjects
A Wu
Publications and source records attributed to A Wu.
Radiosurgery and brain tolerance: an analysis of neurodiagnostic imaging changes after gamma knife radiosurgery for arteriovenous malformations.
In order to analyze complications and the factors responsible for the development of serial imaging changes after stereotactic radiosurgery for intracranial arteriovenous malformations, we reviewed serial post-treatment magnetic resonance imaging scans in 72 patients. Median follow-up was 23 months (range 12 to 35 months). Twenty patients developed post-radiosurgical imaging changes consisting of new regions of increased T2 signal on magnetic resonance imaging in brain surrounding the arteriovenous malformation (two year actuarial incidence of 31%). Imaging changes were associated with headache or new neurological deficits in nine of these 20 (45%) and remained asymptomatic in 11 (55%). Symptoms developed in three of 13 patients with imaging changes in the cerebral cortex or cerebellum, in contrast to six of seven patients who had symptoms with imaging changes in the brainstem (p = .028). The onset of imaging changes varied from five to 18 months after radiosurgery (median, 12 months). Serial follow-up scans four to 25 months after the onset of imaging changes were available for review in 16 patients. Post-radiosurgical imaging changes completely resolved within 4 to 19 months in ten patients and have not yet completely resolved after 6 to 25 months in six patients. The projected actuarial rate for resolution of imaging changes was 88%, 19 months after onset; the median time for resolution was 14 months. Univariate analysis revealed that the development of imaging changes was significantly associated with treatment volume (p = .025), the risk predicted from the integrated logistic formula (p = .042), and the number of isocenters treated (p = .042). In multivariate analysis, volume was the only factor significantly associated with the development of imaging changes.
High energy photon beam percent depth dose curves.
The percent depth dose of 8 MV and 18 MV photon beams were measured for various field sizes. The percent depth dose curves exhibited crossed over at selective depth in phantom. Hence, the percent depth dose increases at shallower depth, is independent at crossed over depth, and decreases at deeper depth with decreasing field size. This peculiar phenomenon, which cannot be explained using the primary and scattered radiation concept, should be noted.
Determination of basal dose rates in Paris system of interstitial implants.
The isodose distributions are related to the source configurations in the Paris system of interstitial implants. In this system, the basal dose rates are determined at those points identified relative to the implant. Once these points have been located, the basal dose rates are merely the summation of the dose rate contributions from all the sources. By applying the symmetry properties of the implant, the number of basal dose rate computations and the number of dose rate summations are reduced. The reduction in both the number of computations and the number of summations has facilitated the determination of the average basal dose rate. After the average basal dose rate has been determined, the reference dose rate that is used clinically is calculated. Examples of determining the basal dose rates for a few interstitial implants are presented.
Various wedge isodose angles for treatment planning.
Various wedge isodose angles or simply wedge angles smaller than the nominal wedge angle were created by combining the isodose distributions generated from a single physical wedge with the isodose distributions of the open field for the 8-MV photon beam. The particular wedge angle generated depends on the weights imposed on these isodose distributions. The relationship between these weights and the wedge angle were examined and found to be nonlinear. The difference between the wedge angles defined at 10 cm depth and those defined using the 50% isodose curve is less 6 degrees. The present data was fitted using two proposed empirical equations.
Wedge filter effects on dosimetric parameters of a linear accelerator.
The open-field and wedged-field output factors as a function of field size for two linear accelerators were measured. Wedge factors were determined by taking the ratio of the outputs with and without the wedge filter. For one linear accelerator, the difference in the output factors between the wedged field and open field can be as large as 5%. The wedge factor for this linear accelerator also varies with the field size. On the other hand, the other linear accelerator shows smaller variation of output factors between wedge field and open field. The variation of wedge factor is less than 1% for a 60 degree wedge. In addition to modifying the isodose distributions, the wedge filter also changes the percent depth dose curves, the output factor, and the wedge factor. The degree of wedge effects on these dosimetric parameters is different for different linear accelerator.
Probing the molecular architecture of (1,3)-beta-glucan (callose) synthase: polypeptide depletion studies.
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The pharmacokinetics of prophylactic antibiotics in trauma.
Despite prophylactic antibiotic use in abdominal trauma patients, infection rates remain high. A previous study from our institution indicated that higher doses of prophylactic antibiotics in trauma patients could significantly reduce subsequent infection rates. To determine if this resulted from altered pharmacokinetic profiles, we performed individualized pharmacokinetic analysis of the prophylactic amikacin regimens given to 28 trauma patients undergoing laparotomy. Patients were prospectively randomized to receive a standard regimen of 11 mg/kg of amikacin every 12 hours or to have their regimens adjusted based upon pharmacokinetic analysis. Repeated pharmacokinetic analyses were performed daily for the three-day prophylactic regimen. There was a significant expansion in the apparent volume of distribution for amikacin that correlated with fluid resuscitation. This, along with increased elimination rates, helps to explain the failure to achieve adequate amikacin levels using standard regimens in trauma patients. Such underdosing may contribute to relatively high infection rates following major abdominal injury.
Physics and dosimetry of the gamma knife.
Since 1968, the gamma knife has been one of the major radiosurgical devices. Although approximately 4300 patients worldwide had been treated with the gamma knife units through June 1990, gamma knife installments in the United States are still rather scarce compared to linear accelerators adapted for radiosurgery. This article describes the basic physical characteristics of the gamma knife, patient set-up procedures, the existing treatment-planning system, the measurements of dosimetry and physical parameters, dose delivery accuracy, and quality assurance procedures. It also includes a vision of future developments and improvements in these areas.
Radiobiologic models for radiosurgery.
A series of initial radiobiologic investigations have been performed using three animal models. The baboon model proved to be a valuable technique to assess the in vivo radiobiologic response of single-fraction irradiation doses delivered to the primate brain stem. Multimodality neurodiagnostic testing, including CT, MR imaging, xenon-enhanced CT, evoked potential studies, and analysis of CSF myelin basic protein levels, all of which eventually were correlated with neuropathologic examination, enabled detection of lesions produced with high-dose (150 Gy) radiosurgery as early as 6 weeks. Within the first 6 months after radiosurgery, lower doses (20 Gy, 50 Gy) did not result in clinically or neurodiagnostically detectable lesions. The rat arteriovenous fistula model permits analysis of the delayed histopathologic effects of radiosurgery on an experimentally created fistula designed to mimic an AVM. The rat C6 glioma model is designed to evaluate the effect of radiosurgery in an infiltrative tumor that simulates a human malignant brain tumor. These studies are intended eventually to increase our knowledge about the safety and efficacy of radiosurgery in both the normal and tumor-implanted brains. We believe that such fundamental studies ultimately will improve our ability to reach the goals of radiosurgery: to destroy the target and spare the surrounding brain. Eventually, it may become feasible to achieve these goals by combining radiosurgical technique with both radiation sensitizers (for the treated volume) and brain protectors.
Complementary DNA sequencing: expressed sequence tags and human genome project.
Automated partial DNA sequencing was conducted on more than 600 randomly selected human brain complementary DNA (cDNA) clones to generate expressed sequence tags (ESTs). ESTs have applications in the discovery of new human genes, mapping of the human genome, and identification of coding regions in genomic sequences. Of the sequences generated, 337 represent new genes, including 48 with significant similarity to genes from other organisms, such as a yeast RNA polymerase II subunit; Drosophila kinesin, Notch, and Enhancer of split; and a murine tyrosine kinase receptor. Forty-six ESTs were mapped to chromosomes after amplification by the polymerase chain reaction. This fast approach to cDNA characterization will facilitate the tagging of most human genes in a few years at a fraction of the cost of complete genomic sequencing, provide new genetic markers, and serve as a resource in diverse biological research fields.
Interstitial IR-192 implants of the oral cavity: the planning and construction of volume implants.
The success of radioactive implant therapy for head and neck carcinomas depends critically on careful planning and execution of the implant procedure. In this paper we discuss our experience with oral tongue and floor of mouth implants, and some innovations introduced to facilitate these procedures. Implants were carried out using standard angiocatheters modified with magnetic caps at the open end and terminated with Teflon spacers and lead shot at the closed end. The importance of accurate source placement and careful determination of the target dose rate is discussed with numerical examples. Differential hot-loading of sources is clearly indicated in cases of extension of the lesion to the dorsal or lateral tongue surface. For dorsal surface extension the use of Teflon spacers at the closed ends of the catheters helps to ensure adequate coverage of the target volume with the higher dose region enclosing the demonstrable tumor. All 10 patients implanted with this technique are controlled without recurrence at a median follow-up of 38 months. The two complications observed appeared to be associated with excessive hot-loading of edge plane 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.
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.
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.
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.
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.
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.