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Idiopathic normal-pressure hydrocephalus

Results of shunting in 62 patients

Peter McL. Black

✓ Of 62 patients given shunts for normal-pressure hydrocephalus of idiopathic type, 46.8% showed some improvement and 27.4% enjoyed virtually complete recovery. The best clinical predictor of good response was the complete triad of memory difficulty, gait disorder, and urine incontinence; 61.2% of patients with this combination of symptoms improved. Gait disturbance alone was also accompanied by improvement in two of three patients. An “obstructive” cisternographic radioisotope pattern was not significantly different from a “normal” pattern in predicting a response to shunting. Computerized tomography (CT) showing large ventricles and little atrophy predicted improvement in 11 out of 13 patients. There were five deaths within 3 months of shunting. The complication rate was 35.4%; subdural collections, shunt malfunction, and postoperative seizures constituted the most frequent complications.

These data suggest that continued investigation for better predictions of shunt response is important, but that in the meantime the clinical pattern and cranial CT pattern are the most satisfactory guides to improvement after shunting.

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Peter McL. Black

✓ The Peter Bent Brigham Hospital was established in Boston in 1913. The purchase of the site defined what would become one of the largest medical complexes in the world. This hospital was intended to be a university hospital based on the model created by Johns Hopkins University. The pioneering work of Harvey Cushing while at the Peter Bent Brigham Hospital is briefly touched on.

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Peter McL. Black

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Elizabeth Noll and Peter McL. Black

It has been demonstrated that glial fibrillary acidic protein (GFAP)-positive astrocyte precursors will differentiate in response to application of retinoic acid (RA), whereas GFAP/oligodendrocyte type 2-astrocyte progenitors will be inhibited from differentiating and continue to be mitotically active in the presence of RA. The authors sought to determine if cells taken from glial tumors that were GFAP positive retained the ability to differentiate following application of RA in vitro, as their normal astrocytic counterparts do. Primary cultures of seven astrocytic tumors were observed to have significantly fewer cells following 1 month of continuous exposure to 100 μM RA. Comparisons with sister control cultures indicated that in control conditions the tumor cells had undergone proliferation, whereas the number of cells in the RA-exposed cultures remained closer to the number of cells initially plated. This response to RA was demonstrated to be specific to the astrocytic tumors by virtue of the fact that cultures of normal brain and an anaplastic ependymoma both showed a strong proliferative response to retinoids.

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Karl W. Swann and Peter McL. Black

✓ This review examines the incidence, natural history, diagnosis, prophylaxis, and management of deep vein thrombosis (DVT) and pulmonary embolism (PE) in neurosurgical patients. Recent studies estimate the incidence of postoperative DVT detected by fibrinogen scanning in neurosurgical patients to be 29% to 43%. Specific factors that enhance the risk of venous thromboembolism include previous DVT, surgery, immobilization, advanced age, obesity, limb weakness, heart failure, and lower extremity trauma. Clinical diagnosis of venous thromboembolism is unreliable but can be augmented by noninvasive screening tests such as iodine-125-fibrinogen scanning, Doppler ultrasonography, and impedance plethysmography. As prophylactic measures, mini-dose heparin and external pneumatic compression of the legs have decreased the incidence of DVT in clinical studies of neurosurgical patients. However, no prophylactic measure has been convincingly shown to prevent PE in neurosurgical patients. Thrombi involving the popliteal, deep femoral, and iliac veins appear most likely to cause significant PE. Anticoagulation therapy constitutes standard management of DVT and PE; however, in neurosurgical patients the potential for precipitating intracranial or intraspinal hemorrhage may necessitate vena caval interruption. This appears to be an effective alternative to anticoagulation.

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Peter McL. Black and Paul H. Chapman

✓ In two cases of normal pressure hydrocephalus, the patients suffered transient abducens weakness following a shunting procedure.

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Karl W. Swann, Peter McL. Black and Mary F. Baker

✓ The authors present a retrospective analysis of the management of deep vein thrombosis (DVT) and pulmonary embolism (PE) in neurosurgical patients at the Massachusetts General Hospital from January, 1978, through June, 1982. There were 44 cases of DVT and 13 cases of PE. Management modalities included observation only, femoral vein ligation, inferior vena cava clipping, transvenous placement of an inferior vena cava filter or umbrella, and anticoagulation therapy. Six (75%) of eight patients with symptomatic DVT who were managed by observation alone had subsequent pulmonary emboli, and three (38%) died. Femoral vein ligation was followed by PE in one of four cases and led to significant leg swelling in two others. Neither observation alone nor femoral vein ligation can be recommended as routine management options. Partial inferior vena cava interruption with a De Weese clip, Kim-Ray Greenfield filter, or Mobin-Uddin umbrella all successfully prevented pulmonary emboli. The major problem associated with these methods was leg edema, which occurred in 47% of patients with clip placement, 25% with filter placement, and 21% with a Mobin-Uddin umbrella. Anticoagulation therapy was associated with a complication rate of 29% and a mortality rate of 15%. Fatal PE and paradoxical hypercoagulability with gangrene of a lower extremity were the causes of death. In one patient, hemorrhage into a glioblastoma occurred following discontinuation of anticoagulation therapy when the coagulation parameters were normal.

The authors conclude that: 1) management with observation alone of patients with symptomatic DVT places the patient at risk for the development of life-threatening pulmonary emboli; 2) the safety and timing of therapeutic anticoagulation in postoperative neurosurgical patients or patients with tumors is unclear; and 3) partial interruption of the inferior vena cava with a transvenous filter successfully prevents PE and may represent a safer alternative to anticoagulation therapy.

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E. Scott Conner, Lorraine Foley and Peter McL. Black

✓ This research was directed at the pathophysiology of normal-pressure hydrocephalus. The experimental method consisted of accurate and simultaneous measurement of the pressure within the ventricle and over the cerebral convexity in cats with hydrocephalus but normal ventricular pressure. Hydrocephalus was induced by the intracisternal injection of kaolin. Prior to the induction of hydrocephalus, the difference between the ventricular pressure and the pressure over the convexity (the transmantle pressure) was small (0.27 ± 0.31 cm saline, mean ± standard deviation). After the induction of normal-pressure hydrocephalus in seven animals, there was a statistically significant elevation of the transmantle pressure to 3.4 ± 3.9 cm saline (p < 0.05, Student's paired t-test). There was no similar increase in animals injected with lactated Ringer's solution. This finding supports the theory that it is the transmantle pressure, and not the ventricular pressure, that is the physiological determinant of ventricular dilatation. The theory explains why hydrocephalus can develop and persist despite normal ventricular pressure.

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Rona S. Carroll, Jianping Zhang, Kathleen Dashner, Madhabananda Sar, Elizabeth M. Wilson and Peter McL. Black

✓ The predominance of meningiomas in females, the accelerated growth of these tumors during the luteal phase of the menstrual cycle and during pregnancy, and the association between meningiomas and breast cancer have led to a number of studies examining the potential role of steroids in the growth of meningiomas. The possibility that androgens play a role in meningioma proliferation has been suggested by a small number of investigators. The aim of this study was to examine the expression of androgen receptor messenger ribonucleic acid (mRNA) and correlate it using immunochemistry with the nuclear localization of androgen receptor in a large number of meningiomas. Thirty-nine meningiomas were examined by Northern blot analysis for the presence of measurable amounts of androgen receptor mRNA and eight of these were analyzed by immunohistochemistry for receptor protein. Sixty-seven percent of the meningiomas expressed androgen receptor mRNA. There was a marked predominance of women among the patients whose tumors expressed androgen receptor; 69% were women and 31% were men. The immunohistochemical data correlated with Northern blot analysis of mRNA. The staining was predominantly nuclear, suggesting that the androgen receptor resides in a location that can activate gene expression.

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Peter McL. Black, Rona Carroll, Danuta Glowacka, Kathleen Riley and Kathleen Dashner

✓ The platelet-derived growth factor (PDGF) family consists of subunits A and B and receptors α and β. This paper evaluates the potential role of the homodimer PDGF-BB as a growth factor in meningiomas. It analyzes the expression of messenger RNA in members of the PDGF family in these tumors, measures the growth response of meningiomas to exogenous PDGF-BB in culture, and examines the induction of the c-fos proto-oncogene by PDGF-BB. Northern blot analysis was carried out on tissue from 20 meningiomas to measure the expression of PDGF-A, PDGF-B, PDGF-α receptor (PDGF-α-R) and PDGF-β receptor (PDGF-β-R). All tumors expressed PDGF-A and PDGF-B subunits. Nineteen of the 20 tumors expressed PDGF-β-R and none expressed PDGF-α-R as measured by this technique.

Because the β receptor is selectively sensitive to stimulation by the PDGF-B subunit, these data suggest that meningiomas might be susceptible to stimulation by PDGF-BB. To test this hypothesis, the effect of exogenous PDGF-BB on meningioma growth was evaluated by incubating cells from 10 human meningiomas. Tritiated thymidine incorporation was used to evaluate stimulation of growth over a 48-hour period using PDGF-BB concentrations of 1, 3, or 6 ng/ml. Linear regression analysis and multiple-factor analysis of variance were used to measure PDGF-BB effects. Three of the 10 tumor specimens responded significantly to PDGF-BB, with a three- to sixfold increase in thymidine incorporation over 72 hours of exposure, and there was a significant overall growth-stimulating effect of PDGF-BB in the 10 tumor specimens tested. In the last set of experiments, the functionality of the PDGF-β-R was determined by examining the induction of the proto-oncogene c-fos by PDGF-BB in meningioma cell cultures. A significant increase in c-fos protein was observed 3 hours after PDGF-BB addition.

These findings demonstrate that PDGF-A, PDGF-B, and PDGF-β-R are expressed in meningiomas and suggest that the β receptor is functional: when it is activated, c-fos levels are increased, and an increase in meningioma cell division is observed after the addition of PDGF-BB. These studies support the hypothesis that PDGF acts as a growth factor in meningiomas.