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Biomedical subjects

C B Wilson

Publications and source records attributed to C B Wilson.

At least 19 recordsLinked to original sources

Measurements of blood flow and exchanging water space in breast tumors using positron emission tomography: a rapid and noninvasive dynamic method.

A noninvasive dynamic method for the measurement of blood flow, using 15O-labeled water and positron emission tomography, has been developed and used to study 20 patients with breast carcinoma. The mean tumor flow was 29.8 +/- 17.0 (SE) ml/dl/min of tissue, while normal breast flow was 5.6 +/- 1.4 ml/dl/min of tissue. The exchanging water space of tissue known as the volume of distribution of the tracer (Vd) was also derived. This is defined as the volume of water in tissue that exchanges with a unit volume of water in arterial blood during the period of the study (7 min). The mean tumor Vd was 0.56 +/- 0.15 ml/ml while normal breast Vd was 0.14 +/- 0.05 ml/ml. The low value in normal breast is partly due to the high fat content of the tissue. The mean flow per unit of exchangeable volume was similar in tumor (52.8 +/- 22.0) and normal breast tissue (45.2 +/- 20.0). This suggests that the major discrepancy seen in measured values of flow between breast tumors and normal breast principally reflects the different composition of the two tissues. This method is rapid and suited for studying the reactivity of human tumor vasculature, so extending studies are being performed on animal tumors.

Adult

Cell kinetic analysis of human brain tumors by in situ double labelling with bromodeoxyuridine and iododeoxyuridine.

Fifty-seven patients with brain tumors (29 gliomas, 23 meningiomas, 5 miscellaneous) received infusions of intravenous iododeoxyuridine (IUdR) and bromodeoxyuridine (BUdR) 1-5 hr apart shortly before tumor removal. Excised tumor specimens were stained sequentially for BUdR and IUdR. The percentage of BUdR-labelled cells was determined to establish the labelling index (LI), or S-phase fraction, and the ratio of cells labelled only with IUdR to cells labelled with BUdR or with BUdR and IUdR was determined to calculate the duration of S-phase (Ts) and the potential doubling time (Tp) of each tumor. The BUdR LIs varied from less than 1% to 20%, reflecting the malignancy of each tumor. Despite the difference in LIs, however, Ts was fairly uniform (mean +/- SD, 8.7 +/- 2.0 hr). Tp varied from 2 days to more than 1 month and correlated closely with the BUdR LIs (Tp = 23/LI0.93; r2 = 0.91). Double-labelling studies with IUdR and BUdR allow the S-phase fraction, Ts and Tp to be determined from a single biopsy specimen and thus provide more useful information on the growth characteristics of individual tumors than can be obtained by single-labelling studies with BUdR.

Brain Neoplasms

Histochemical study of pituitary adenomas with Ki-67 and anti-DNA polymerase alpha monoclonal antibodies, bromodeoxyuridine labeling, and nucleolar organizer region counts.

The growth potential of 65 pituitary adenomas was determined by histochemical analysis with Ki-67 and anti-DNA polymerase alpha monoclonal antibodies, bromodeoxyuridine (BrdUdR) labeling, and counts of argyrophilic nucleolar organizer regions (Ag-NORs). The mean proliferating cell indices (PCIs) determined by Ki-67 and anti-DNA polymerase alpha and the BrdUdR labeling index (LI) were generally very low [1.0 +/- 0.2%, 1.1 +/- 0.2%, and 0.5 +/- 0.1% (+/- SE), respectively]. Apart from adrenocorticotropic hormone-positive adenomas, which had significantly higher indices, there were no statistically significant differences in the indices among the other subtypes of pituitary adenomas. Recurrent tumors had higher Ki-67 and DNA polymerase alpha PCIs and BrdUdR LIs (3.6%, 4.2%, 1.4%) than primary tumors (0.8%, 0.8%, 0.3%; P less than 0.005). The number of Ag-NORs did not correlate significantly with any of the three indices. The mean number of Ag-NORs was higher in nonfunctioning adenomas than in functioning adenomas (2.04 vs 1.66, P less than 0.005); among prolactin-positive adenomas, those treated preoperatively with bromocriptine had more Ag-NORs than untreated tumors (1.75 vs 1.57, P less than 0.005). These results suggest that the Ki-67 and DNA polymerase alpha PCIs and the BrdUdR LI predict the growth potential of individual pituitary adenomas, whereas the number of Ag-NORs appears to correlate with hormone production rather than with the proliferative potential.

Adenoma

Highly anaplastic astrocytoma: a review of 357 patients treated between 1977 and 1989.

Between May 1977 and August 1989, 357 patients (199 male, 158 female; median age 40 years) with highly anaplastic astrocytomas other than glioblastoma multiforme were treated according to any of several protocols used in studies by the University of California, San Francisco, and the Northern California Oncology Group. The data evaluated were age, Karnofsky Performance Score, survival, time to tumor progression, therapy, and the effect of treatment at the time of progression. The records of 219 patients were taken from the University of California database, and those of the other 138 were taken from the Northern California Oncology Group computer files. Their median Karnofsky Performance Score was 90% (range 40-100%), the overall median survival was projected as 170.9 weeks, and the median time to first tumor progression was 127.3 weeks. The median survival time measured after the first progression was 41.3 weeks. Age and Karnofsky Performance Score had a significant influence on survival and on time to the first tumor progression, whereas extent of surgery and the use of interstitial brachytherapy in the initial therapy did not. We conclude that these patients can expect a median survival of over 3 years, that young age and high Karnofsky Performance Score have a positive influence on survival, and that salvage therapies can extend survival after the onset of tumor progression for nearly a year. Although it did not lengthen survival when used in initial therapy, interstitial brachytherapy used at the time of tumor progression was associated with increased survival.

Adolescent

Re-irradiation of pituitary adenoma.

Fifteen patients initially irradiated for pituitary adenoma were subsequently treated with a second course of radiotherapy at the University of California at San Francisco between 1961 and 1989. The re-irradiation followed surgery in all but two cases. The median time to recurrence was 9 years (range 2-17) and median follow-up after the second course of radiotherapy was 10 years (range 1-30). The median initial radiation dose was 4084 cGy; that at recurrence was 4200 cGy. Local control has been maintained in 12 patients. One failed locally with a benign adenoma that was surgically salvaged. Two developed pituitary carcinomas which were poorly controlled. Of the patients who presented with visual abnormalities at the time of recurrence, 50% improved and the remainder stabilized after re-irradiation. There are no long-term visual complications. Hypopituitarism was present in nine patients prior to the second course of radiotherapy and developed in the remaining six patients after re-irradiation. Temporal lobe injury was seen in two patients. Careful analysis of each patient's pituitary and temporal lobe doses, intervals between treatments, treatment volume, neurets, relative decay factors, absolute decay factors, TDF and modified LQF values, and dose-volume relationships, revealed no correlation with complication or likelihood of local control. Repeat radiotherapy for recurrent pituitary adenoma with the doses used in these patients appears to carry acceptable risk with good local control.

Adenoma

Interstitial brachytherapy for newly diagnosed patients with malignant gliomas: the UCSF experience.

Although interstitial brachytherapy appears to be effective in treating recurrent malignant gliomas, it has been studied less extensively in patients with newly diagnosed tumors. To examine the effect of this treatment when used at the time of primary diagnosis, we retrospectively reviewed the records of 88 patients who received temporary interstitial implants of 125I for newly diagnosed malignant gliomas. This brachytherapy was preceded by a course of external radiation therapy and followed, in some cases, by chemotherapy. The median duration of survival after the beginning of external radiation therapy was 87 weeks in patients with glioblastoma multiforme and 160 weeks in those with anaplastic gliomas. In 46% of patients with glioblastoma multiforme and 56% of those with anaplastic gliomas, a second operation was necessary to remove symptomatic radiation necrosis, recurrent tumor, or both. Our results support the conclusion that interstitial brachytherapy used at the primary diagnosis lengthens survival in selected patients with glioblastoma multiforme. However, the toxicity is significant in terms of the need for surgical resection of symptomatic necrosis. In patients with anaplastic gliomas, the toxicity associated with the treatment probably outweighs its advantages.

Adolescent

The effect of type-specific polysaccharide capsule on the clearance of group B streptococci from the lungs of infant and adult rats.

To study the importance of the type-specific polysaccharide capsule of group B streptococci (GBS) in the pathogenesis of lung infections, bacterial clearance rates and lung cellular responses to encapsulated and unencapsulated variants of types III and Ia GBS strains were investigated in rats. Bacteria were instilled by direct intratracheal inoculation to simulate aspiration during parturition. Neonates failed to eliminate encapsulated or unencapsulated GBS strains within 6 h of inoculation, whereas adults cleared greater than 90% of each strain within 6 h. Neutrophils accumulated rapidly in the lungs of neonates and adults in response to all GBS strains. Immediately after inoculation, neonatal alveolar macrophages contained fewer encapsulated GBS than did adult alveolar macrophages and fewer encapsulated than unencapsulated GBS, suggesting that the capsule impairs the initial phagocytosis of GBS in the lungs of neonates. Animal age was a more important determinant of bacterial elimination from the lung than the type-specific GBS capsule. However, both age and the bacterial capsule were important determinants of systemic dissemination.

Animals

Diminished interferon-gamma and lymphocyte proliferation in neonatal and postpartum primary herpes simplex virus infection.

Interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha production and lymphocyte proliferation in response to herpes simplex virus (HSV) antigen were assessed in 13 neonates and 3 parturient women with primary HSV infection. In comparison with 9 nonparturient adults, the neonates and parturient women showed significantly (P less than .01) diminished HSV antigen-stimulated lymphocyte proliferation and IFN-gamma production in the first 3-6 weeks after onset of infection. TNF alpha production did not differ significantly among HSV-infected groups. The impairment in neonatal cellular immunity was due, at least in part, to a specific deficit in response to HSV antigen. Lymphocyte proliferation and TNF alpha production in response to the mitogen concanavalin A (ConA) were comparable in adults and infants, but ConA-stimulated IFN-gamma production in infants was diminished throughout the study period. In contrast, HSV antigen-stimulated IFN-gamma production was comparable in infants and adults after 6 weeks. Not all patients with diminished cellular immune responses to HSV antigen manifested severe clinical disease. Nevertheless, patients with significant clinical morbidity had diminished cellular immune responses to HSV antigen. These results suggest that delayed acquisition of antigen-specific cellular immunity in primary HSV infection predisposes to more severe clinical disease.

Antibodies, Viral

Advances in diagnostic techniques of pituitary tumors and prolactinomas.

The main advances in the diagnostic evaluation of pituitary tumors and prolactinomas have been in the areas of improved magnetic resonance techniques and in the use of inferior petrosal sinus sampling. New dynamic techniques of rapid acquisition magnetic resonance imaging during bolus contrast infusion have improved the sensitivity for the diagnosis of the small microadenoma. The development of three-dimensional volume imaging has also led to a further improvement in sensitivity to small lesions of the sella. The measurement of adrenocorticotropin levels in the inferior petrosal sinus in patients with Cushing's syndrome assists in the differentiation of adrenocorticotropin-secreting pituitary tumor from other peripheral causes of the syndrome. The use of corticotropin-releasing hormone concomitant with sampling has proven to be of value in improving sensitivity and specificity. Elevated levels of growth hormone in petrosal sinus sampling have also been shown to be valuable in the early diagnosis of acromegaly when peripheral hormone levels and imaging are nondiagnostic.

Adenoma

Decreased granulocyte-macrophage colony-stimulating factor production by human neonatal blood mononuclear cells and T cells.

Impaired production and delivery of neutrophils to the site of infection have been implicated in the increased susceptibility of the neonate to infection. Because granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) play critical roles in the production of neutrophils from marrow precursors, we assessed the ability of leukocytes from neonates and adults to produce GM-CSF, G-CSF, and, for comparison, macrophage colony-stimulating factor (M-CSF) after stimulation with concanavalin A +/- phorbol myristate acetate [blood mononuclear cells (MC) and T lymphocytes] or lipopolysaccharide (monocytes). MC and monocytes from adult and neonatal subjects produced mRNA for GM-CSF, G-CSF, and M-CSF, whereas T cells produced only GM-CSF mRNA. Neonatal MC and T cells accumulated only approximately 30% as much GM-CSF mRNA as did adult MC and T cells. In contrast, the accumulation of GM-CSF mRNA by neonatal and adult monocytes was similar. Neonatal MC also accumulated similar amounts of G-CSF mRNA and somewhat more M-CSF mRNA than did adult MC; results with monocytes were similar to those with MC. Results of colony-stimulating activity bioassays on supernatants from neonatal and adult MC stimulated with concanavalin A paralleled the mRNA results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Late manifestations of esthesioneuroblastomas in the central nervous system: report of two cases.

Two patients with esthesioneuroblastomas that disseminated in the central nervous system (CNS) and elsewhere are reported. The latest recurrences in the CNS were 19 years after the diagnosis in patient and 9 years after the diagnosis in the other. Because the treatment of patients with such late recurrences is complicated by previous surgical procedures and radiation therapy, we review therapeutic options for these patients. The literature has not previously stressed the occurrence of late metastases, including those to the CNS, after prolonged disease-free intervals.

Adolescent

Radiologic characteristics and results of surgical management of Rathke's cysts in 43 patients.

Although Rathke's cysts are a relatively common autopsy finding, rarely have they been reported as a clinical entity. Because of recent improvements in neuroradiological imaging, cystic intrasellar and suprasellar lesions are discovered often, leading to questions about proper management. Against this background, we reviewed the data from 43 patients with Rathke's cysts treated by one neurosurgeon over a 13-year period, and present the results here. The 43 patients had a mean age of 34 years, and 77% were female. Headache was the most common symptom, followed by galactorrhea, visual field loss, and hypopituitarism. Computed tomographic (CT) scans were reviewed in 20 cases, magnetic resonance (MR) images were reviewed in 15, and both CT and MR studies were reviewed in 5 cases. Although all Rathke's cysts were discrete and well-defined by both CT and MR imaging, the diversity of locations, CT attenuations, and MR signal intensity make it difficult to establish the diagnosis by radiological criteria. Forty patients underwent transsphenoidal surgery and three underwent craniotomy. There was one recurrence at 25 months requiring a second operation, and the mean follow-up period was 62 months. Seven patients had persistent headaches. For symptomatic lesions suspected to be Rathke's cysts, the recommended treatment is simple drainage of the cyst with biopsy of the wall, when this can be done safely. Follow-up imaging should be minimal for asymptomatic patients, and radiation therapy is not indicated.

Adolescent

Meningiomas: clinical implications of a high proliferative potential determined by bromodeoxyuridine labeling.

The clinical behavior of meningiomas with a high proliferative potential was analyzed to determine if the bromodeoxyuridine (BUdR) labeling index (LI) could be used to predict recurrence and the time to reoperation. Each patient received an intraoperative infusion of BUdR to label cells in DNA synthesis; the percentage of S-phase cells, or BUdR LI, of each tumor was determined immunohistochemically. Of 178 meningiomas studied, 53 had BUdR LIs greater than or equal to 1%. Of these 53 tumors, 21 were diagnosed histopathologically as malignant meningioma. Twenty-two percent of nonmalignant tumors and 81% of malignant tumors were recurrent or recurred after the BUdR study; repeat studies were performed in four patients. The mean BUdR LI of recurrent tumors was significantly higher than that of the nonrecurrent tumors [3.9 +/- 2.6 versus 1.9 +/- 1.0% (SD), P less than 0.005]. The recurrence rate was 100% for tumors with LIs greater than or equal to 5%, 55.6% for those with LIs of 3 to 5%, and 30.6% for those with LIs of 1 to 3%; the percentages of malignant meningiomas in these groups were 88%, 78%, and 19%, respectively. Logarithmic regression analysis showed that the time to reoperation (in months) can be predicted from the BUdR LI as: 70.0 x LI (%)-1.2 (R = 0.76). This formula can be used to estimate the doubling time of individual tumors and to predict the period of greatest risk of recurrence of meningiomas with a high proliferative potential.

Adolescent

Magnetic resonance imaging of tuberculum sellae meningiomas: preventing preoperative misdiagnosis as pituitary macroadenoma.

Despite recent advances in neurodiagnostic imaging, it may be difficult to differentiate tuberculum sellae meningiomas from pituitary macroadenomas preoperatively. Magnetic resonance (MR) imaging has supplanted computed tomography as the imaging modality of choice for sellar and parasellar lesions, but unenhanced MR imaging does not reliably distinguish between all tuberculum sellae meningiomas and pituitary macroadenomas. Accurate differentiation between these alternative diagnoses of a suprasellar mass is important because a tuberculum sellae meningioma always requires a craniotomy, whereas a transsphenoidal route is preferred for removing most pituitary macroadenomas. The gadolinium-enhanced MR images of seven patients with tuberculum sellae meningioma and seven with pituitary macroadenoma were reviewed retrospectively. Although no specific radiological feature was pathognomonic, a combination of several features allowed the correct diagnosis in all cases. Three characteristics of tuberculum sellae meningiomas distinguish them from pituitary macroadenomas: 1) bright homogeneous enhancement with gadolinium, as opposed to heterogeneous, relatively poor enhancement; 2) a suprasellar rather than a sellar epicenter of tumor; and 3) tapered extension of an intracranial dural base. Each of these findings can be subtle, but careful examination of gadolinium-enhanced, high-quality, thin section coronal and sagittal MR images of the parasellar region for this constellation of findings will allow the correct preoperative diagnosis in patients with either of these tumors.

Adenoma