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Biomedical subjects

C B Wilson

Publications and source records attributed to C B Wilson.

At least 253 records · Page 14Linked to original sources

Variability in the proliferative potential of human gliomas.

One hundred forty-three patients with gliomas of astrocytic origin (61 with glioblastomas multiforme (GM) and 82 with astrocytomas) received an intravenous infusion of bromodeoxyuridine (BUdR), 150-200 mg/m2 at the time of surgery, to label tumor cells undergoing DNA synthesis. BUdR-labeled cells were identified by the indirect immunoperoxidase method using anti-BUdR monoclonal antibodies. The percentage of BUdR-labeled cells, or BUdR labeling index (LI), was calculated by microscopic examination of selected viable areas of the tissue sections. The GMs had a median LI of 7.5%, and three quarters of these tumors had LIs greater than 5%. Highly anaplastic astrocytomas (HAAs) and moderately anaplastic astrocytomas (MoAAs) had median LIs of 2.3% and less than 1%, respectively. Among the HAAs, the LI was 1% to 5% in 56% of tumors, greater than 5% in 26%, and less than 1% in 18%. More than 60% of MoAAs had LIs less than 1%, which agrees with the slow clinical progression of this type of tumor, and the remainder had LIs of 1.4% to 9.3%. These results show that histopathologically similar tumors may have different proliferative potentials. Measuring the proliferative potential of individual gliomas is therefore crucial for predicting the prognosis more accurately and for devising more tumor-specific treatment regimens for individual patients.

Astrocytoma↗

The role of lymphocytes and monocytes in hematopoietic growth factor production by peripheral blood mononuclear cells.

Stimulated peripheral blood mononuclear cells (MNC) are one of the richest described physiologic sources of colony-stimulating activity. To understand the molecular basis for, and the cellular sources of, this MNC activity, we cultured purified human lymphocytes and monocytes for 2 hr to 6 days and examined colony-stimulating factor (CSF) gene activity by Northern blot analysis. We show that MNC are capable of expressing messenger RNA for macrophage (M)-CSF, granulocyte (G)-CSF, GM-CSF, and multi-CSF when stimulated with mitogens. The time courses of induction of these genes differ, with G-CSF induction preceding that of the other CSFs. In addition, the spectra of CSFs produced by cell populations enriched for lymphocytes, monocytes, or macrophages differ. The implications of these findings for the selective activation of hematopoiesis are discussed.

Cells, Cultured↗

Postoperative radiotherapy of primary spinal cord tumors.

During the 30 year period from 1957 to 1986, 42 patients with primary tumors arising from the spinal cord or cauda equina received postoperative irradiation at the University of California, San Francisco. Twenty-one patients had ependymomas: 18 were localized to one site, and 3 diffusely involved the cord. There were 12 patients with low grade astrocytomas and 3 with highly anaplastic astrocytoma or glioblastoma multiforme. All astrocytomas were localized at presentation. In 6 cases tissue was insufficient to permit a histologic diagnosis. Thirty-nine patients (93%) received total radiation doses ranging between 45.0-54.7 Gy using standard fractionation. The 10-year actuarial disease-specific survival rate for patients with localized ependymoma was 93%; 33% of these tumors recurred locally. The corresponding rate for diffuse ependymomas was 50%; the spinal disease was controlled in all 3 patients, but one developed a cerebral metastasis despite prophylactic cranial irradiation. Low-grade astrocytoma patients had a 10-year actuarial disease-specific survival rate of 91%, with 33% of these tumors recurring locally. No patient with highly anaplastic astrocytoma or glioblastoma multiforme survived longer than 8 months; all of these tumors recurred locally, and two of the three also developed diffuse craniospinal axis metastases. Local recurrence for ependymoma was delayed as long as 12 years following treatment, while all but one astrocytoma failure occurred within 3 years of treatment. No significant dose-response relationship with respect to local control was noted for either localized ependymomas or low grade astrocytomas. One patient developed radiation myelitis after receiving 50.4 Gy with standard fractionation. These results indicate that patients who undergo postoperative irradiation for low grade spinal astrocytomas and localized spinal ependymomas achieve excellent survival. However, despite treatment with total radiation doses taken to the practical limit of spinal cord tolerance, local failure remains common.

Adolescent↗

Sex and the single kidney.

Micropuncture measurements revealed that approximately 9 to 10 months after uninephrectomy and maintenance on a high-protein diet, glomerular capillary BP was significantly higher in male than in virgin female rats. This might account for the greater susceptibility of the male to age- and ablation-induced glomerular damage reported by others, although at the time of the present studies, significant reduction in function and worsening in glomerulosclerosis in males v females was barely evident. In a second group of chronically uninephrectomized females, the effects of multiple (five) consecutive pregnancies and lactations were investigated and did not indicate any severe deleterious long-term effects of pregnancy on the glomeruli in this model of underlying renal compromise. Variable responses to an acute intravenous glycine challenge which did not correlate well with the extent of glomerular damage were observed in each group, suggesting that this test may not always be informative regarding underlying glomerular disease.

Animals↗

The effect of halothane, isoflurane, or sufentanil on the hypertensive response to cerebellar retraction during posterior fossa surgery.

The blood pressure (BP) response to cerebellar retraction during microvascular decompression of the fifth cranial nerve was investigated in 26 ASA physical status 2 or 3 patients with trigeminal neuralgia. One surgeon performed all operations. To determine the effect of three anesthetic techniques on the BP response, patients were randomly assigned to receive halothane, isoflurane, or sufentanil in sufficient doses with 60% nitrous oxide to achieve a precerebellar retraction systolic BP that was 10-20% below the average ward systolic BP (as per standard clinical practice). The resultant doses were halothane 1.65 +/- 0.27 (mean +/- SD) MAC, isoflurane 1.56 +/- 0.17 MAC (P greater than 0.05), and sufentanil 2.7 micrograms/kg (MAC values include 0.6 MAC contribution from 60% nitrous oxide). In all patients BP increased during the cerebellar retractor placement period compared with the preretractor placement period (P less than 0.05). The peak increase in systolic BP in response to cerebellar retraction was 17 +/- 6 mmHg for halothane, 38 +/- 20 mmHg for isoflurane, and 26 +/- 19 mmHg for sufentanil. The difference between halothane and isoflurane was significant (P less than 0.05). Mean and diastolic BP showed similar significant differences. The authors conclude that halothane attenuates the hypertensive response to cerebellar retraction more than isoflurane when administered in approximately 1.6 MAC concentrations (MAC value includes contribution from nitrous oxide).

Aged↗

Transluminal angioplasty of intracerebral vessels for cerebral arterial spasm: reversal of neurological deficits after delayed treatment.

We used intracerebral transluminal angioplasty to treat two episodes of symptomatic vasospasm in a patient recovering from an aneurysmal subarachnoid hemorrhage. The procedures were performed after medical therapies, intravascular volume expansion, and induced arterial hypertension failed to alleviate the patient's neurological condition. The first angioplasty, confined to the right middle cerebral and distal internal carotid arteries, took place more than 30 hours after the onset of left hemiplegia. Despite the subsequent discovery of a small parietal lobe infarct, it brought about a marked improvement in left motor function and may have also limited the spread of necrotic damage. The second angioplasty was necessitated when stenotic segments of the basilar and posterior cerebral arteries caused a 24-hour decline in the patient's mental status. Although delayed in relation to the onset of symptoms, it successfully reversed the patient's comatose state. The use of transluminal angioplasty for vasospasm is generally limited to cases where it can be performed shortly after the onset of neurological symptoms; delaying the procedure increases the risk of hemorrhage from reperfused areas of infarction. Our experience with this patient demonstrates that delayed angioplasty can improve vascular flow to ischemic territory, even after infarction, without complications and with resultant improvement in neurological function.

Angioplasty, Balloon↗

Tubuloglomerular feedback activity after glomerular immune injury.

Tubuloglomerular feedback responses were examined in control euvolemic and glomerulonephritic rats 4 wk after administration of antiglomerular basement membrane antibody (AGBM). Single-nephron glomerular filtration rate (SNGFR) was reduced approximately 30% in AGBM rats. Tubuloglomerular feedback responses were also tested with both artificial and native tubular fluid. SNGFR was evaluated at 0, 10, 20, 30, and 40 nl/min. Tubuloglomerular feedback response was present in both control and AGBM rats, although there was a shift in turning point or perfusion rate down and leftward at which SNGFR decreased in the AGBM rats. No difference in tubuloglomerular feedback responses was observed between artificial and native tubular fluids. In this model of moderate glomerulonephritis, tubuloglomerular feedback activity appears to be appropriate and intact, and the composition of the fluid entering the loop of Henle does not appear to determine or to be a condition for the presence or absence of tubuloglomerular feedback activity.

Animals↗

Human pituitary tumors secrete chromogranin-A.

Chromogranin-A (CgA) has emerged as a serum and tissue marker for a number of endocrine tumors. We studied 15 patients with pituitary tumors to evaluate the clinical value of CgA as a serum and tissue marker for such tumors. One third of the patients had elevated serum CgA levels; 2 of these patients had nonsecreting pituitary tumors, and the other 3 had corticotroph adenomas. CgA-positive cells were detected in 9 of the 11 anterior pituitary tumors that were immunostained; in these 9 tumors at least half of the cells were CgA positive. We conclude that CgA production is common in pituitary tumors and that immunohistochemical studies for CgA may aid in their classification. In addition, serum CgA measurements may help to identify patients with pituitary tumors, especially those that do not secrete a known pituitary peptide.

Biomarkers, Tumor↗

High-resolution MR imaging of pituitary microadenomas at 1.5 T: experience with Cushing disease.

The MR images of 27 patients with clinically and biochemically suspected Cushing disease were evaluated retrospectively in a blinded fashion. The MR interpretation was compared with detailed operative diagrams and operative and pathologic reports. The examinations were performed on a 1.5-T MR system with thin-section sagittal and coronal T1-weighted (short TR/TE) images. Each pituitary half was considered separately (54 "halves"). Twenty-one pituitary halves were considered to have glandular abnormalities on MR. Compared with surgical findings, 17 MR findings were true positives and four were false positives (one pars intermedia cyst, three normal tissue). Of the 33 pituitary halves considered normal on MR, 26 were true negatives and seven were false negatives. MR had an overall sensitivity of 71% and a specificity of 87% for these adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. A focal glandular hypointensity identified on coronal images was the most sensitive predictor of adenoma location. Sagittal images were not useful in either detection or localization. Upward convexity of the gland and deviation of the stalk were less useful indicators. Abnormalities of the sellar floor were the least reliable. In comparison with the capabilities of CT detection of microadenomas described in the current literature, it appears that high-field thin-section MR of the sella is the most sensitive imaging method for preoperative localization of ACTH-secreting adenomas in patients with Cushing disease.

Adenoma↗

Hyperfractionated radiation therapy for brain-stem glioma: a phase I-II trial.

Fifty-three patients (19 adults and 34 children) harboring brain-stem glioma were treated with hyperfractionated radiation therapy (100 cGy twice a day, 5 days/wk, to a total dose of 7200 cGy). For the entire group, the median time to tumor progression (TTP) was 59 weeks (adults 66 weeks, children 44 weeks) and the median survival time was 74 weeks (adults 92 weeks, children 64 weeks). Statistically significant prognostic factors associated with a decrease in TTP and median survival times (adults less than children) were: patient's age, a clinical history of less than 2 months, widespread brain-stem dysfunction, and a diffuse tumor as seen on magnetic resonance imaging. A finding of glioblastoma multiforme at histological analysis was associated with a statistical trend toward poorer survival, but in general tumor histology was not predictive of outcome. No evidence of an increase in acute or delayed radiation toxicity was seen with this fractionation schedule and total dose. This study suggests that hyperfractionation prolongs the TTP and survival time for many patients with brain-stem glioma. However, there remains a group of patients who are only moderately helped by this technique and for whom more aggressive treatment is warranted.

Adult↗

Correlation of histopathological features and proliferative potential of gliomas.

One hundred fifty-two intracranial gliomas of various types were reviewed in order to correlate the histopathological features with the proliferative potential of each tumor as reflected by the bromodeoxyuridine (BUdR) labeling index (LI). Patients undergoing surgical removal of gliomas were given a 30-minute intravenous infusion of BUdR (150 to 200 mg/sq m) to label S-phase tumor cells. The tumor specimens were stained immunohistochemically for BUdR and processed for routine histopathological diagnosis. The BUdR LI was calculated as the percentage of labeled cells among cells analyzed. Twenty-seven histological features in three categories (degenerative, vascular, and cellular changes) were considered. A significantly higher BUdR LI (p less than 0.05) was found in tumors with necrosis than in those without this feature; tumors with both coagulative and liquefactive necrosis had the highest BUdR LI (p less than 0.05). Increased vascularity was also associated with a higher BUdR LI (p less than 0.05). Although tumors with abnormal mitotic figures had a significantly higher BUdR LI than those without, the number of mitoses did not correlate with a higher BUdR LI. These results suggest that the number of mitoses is not a good indicator of tumor growth rate. Necrosis and increased vascularity should be heavily weighted in predicting the proliferative potential of individual gliomas.

Adult↗

Prognostic implications of the bromodeoxyuridine labeling index of human gliomas.

This study includes 182 patients with intracranial gliomas who received bromodeoxyuridine (BUdR), 200 mg/sq m intravenously, at the time of craniotomy but before tumor biopsy. The tumor specimens were stained for BUdR using the immunoperoxidase method; the BUdR labeling index (LI), or S-phase fraction, was calculated as the percentage of BUdR-positive cells. The median BUdR LI's for 127 primary moderately anaplastic astrocytomas, highly anaplastic astrocytomas, and glioblastomas (less than 1%, 2.7%, and 7.3%, respectively; range 0% to 38.1%) were not significantly different from those of 55 similar recurrent tumors (less than 1%, 4.3%, and 7.4%, respectively; range 0% to 30.5%). The mean LI was significantly higher in tumors from patients over 50 years of age than in tumors from younger patients (p less than 0.001). The age-related difference in LI's was found in both groups of patients with astrocytomas but not in those with glioblastomas. Kaplan-Meier survival curves showed a significantly greater probability of survival among patients whose tumors had LI's of less than 1% than among those with LI's greater than 5%; survival probability of patients with tumor LI's of 1% to 5% was intermediate between the two extremes. Thus, the BUdR LI appears to reflect the proliferative potential more accurately than the histopathological diagnosis and should therefore be considered an important factor in determining the prognosis of individual patients with intracranial gliomas and in selecting their treatment.

Astrocytoma↗

Complex dural arteriovenous fistulas. Results of combined endovascular and neurosurgical treatment in 16 patients.

Of the 88 patients evaluated for symptomatic dural arteriovenous (AV) fistula over the past 8 years, 16 had large or complicated lesions that could not be treated with standard transvascular approaches or in which such treatment had been unsuccessful. Eleven fistulas were located in the transverse sinus, two in the cavernous sinus, two in the straight sinus, and one in the falx-tentorial region near the vein of Galen. The patients were treated with a combination of endovascular and neurosurgical techniques. Fourteen patients underwent preoperative transarterial embolization; this procedure closed the fistula in one patient. In the remaining 15 patients, surgery was performed to provide access to the fistula for embolization from either the venous or the arterial side, or for excision of the fistula. Transvenous embolization completely obliterated the fistula in seven of nine patients; the fistulas were embolized incompletely through the feeding arteries in two patients; and complete surgical resection of the lesion was accomplished in four patients. Complications related to venous occlusion occurred in two patients and one patient suffered communicating hydrocephalus that was effectively treated by shunting. There were no deaths. The results suggest that combined endovascular and neurosurgical techniques are a safe and effective means for the treatment of selected complex dural AV fistulas.

Adult↗

Evaluation of microvascular decompression and partial sensory rhizotomy in 252 cases of trigeminal neuralgia.

Outcome after 252 posterior fossa explorations for the treatment of trigeminal neuralgia was determined by a retrospective review. Patients with distortion of the fifth nerve root caused by extrinsic vascular compression underwent microvascular decompression, those with no compression underwent partial sensory rhizotomy, and those with vascular contact but no distortion of the nerve root underwent decompression and rhizotomy. The mean follow-up period was 5.1 years. An excellent (75%) or good (8%) clinical outcome was achieved in 208 patients; 13 patients (5%) experienced little or no pain relief. Thirty-one patients (12%) suffered recurrent trigeminal neuralgia an average of 1.9 pain-free years after operation; recurrence continued at a rate of approximately 2% per year thereafter. Reoperation for recurrent or persistent pain provided excellent or good results in 85% of reoperated patients, but partial sensory rhizotomy was required in most of these patients. Outcome was affected by previous surgical procedures. A previous percutaneous radiofrequency lesion was associated with a significantly greater incidence of fifth nerve complications and a worse outcome after posterior fossa exploration. Because of this finding, the authors recommend that percutaneous radiofrequency rhizolysis be reserved for patients who have failed posterior fossa exploration or who are not candidates for surgery. Patients with compressive nerve root distortion and a short duration of symptoms before surgery had a significantly better outcome than patients with a longer duration of symptoms. In contrast, there was no relationship between the duration of symptoms and outcome of patients without nerve root distortion. Vascular decompression may cause dysfunction of the trigeminal system in tic douloureux, but in patients who remain untreated for long periods an intrinsic abnormality develops that may perpetuate pain even after microvascular decompression. Posterior fossa exploration is recommended as the procedure of choice for patients with trigeminal neuralgia who are surgical candidates.

Humans↗

Glomerular effects of pregnancy in a model of glomerulonephritis in the rat.

These studies were designed to investigate the functional and morphologic glomerular effects of pregnancy in a model of experimentally induced glomerulonephritis (GN) in the Munich-Wistar rat. Virgin and midterm (day 12) pregnant rats were studied during the autologous phase of anti-glomerular basement membrane antibody GN and were compared with normal control virgin and pregnant rats. In this model of moderately intense GN, glomerular filtration rate (GFR) and single-nephron GFR were not different from normal controls; however, glomerular micropuncture revealed that glomerular capillary blood pressure was elevated and the glomerular capillary ultrafiltration coefficient, Kfi, was reduced in rats with GN compared with normal rats. In addition a substantial proteinuria was present, and there was morphologic evidence of a moderate and fairly uniform GN. The superimposition of pregnancy to midterm (11 to 13 days) had no effects on the proteinuria or glomerular morphology in rats with GN. Also, pregnancy did not further alter the increased glomerular blood pressure or reduced Kf that occur in this model of GN. Despite the presence of an underlying glomerular disease, the maternal kidney was able to increase renal plasma flow. When underlying mild GN is present, 11 to 13 days of pregnancy does not appear to worsen the disease in the short term. Other studies are needed to determine the long-term renal effects of repeated pregnancy when underlying GN is present.

Animals↗