Raymond N. Kjellberg

Pregnancy and the Risk of Hemorrhage from Cerebral Arteriovenous Malformations

We conducted a retrospective analysis of 451 women with an arteriovenous malformation (AVM) of the brain to determine whether pregnancy is a risk factor for cerebral hemorrhages. A total of 540 pregnancies occurred among our patient population, resulting in 438 live births and 102 abortions. There were 17 pregnancies complicated by a cerebral hemorrhage. The hemorrhage rate during pregnancy for women with an unruptured AVM was 0.035 +/- 0.005 per person-year. The hemorrhage rate for nonpregnant women of childbearing age with an unruptured AVM was 0.031 +/- 0.002 per person-year. Pregnancy did not increase significantly the rate of first cerebral hemorrhage from an AVM (P = 0.35). We found that women with an AVM face a 3.5% risk of hemorrhage during pregnancy. Pregnancy is not a risk factor for hemorrhage in women without a previous hemorrhage. This conclusion assumes no selection bias exists in our study population; a bias would be introduced if the risk of fatal outcome after a hemorrhage were greater in pregnant women than in nonpregnant women.

PROTON-BEAM THERAPY IN ACROMEGALY.

Abstract Bragg-peak proton hypophysectomy was used in 22 acromegalic patients. Of 14 followed for two to 36 months, size of hands, feet or face decreased in nine. Variable improvement took place in...

Estradiol treatment of acromegaly Reduction of immunoreactive somatomedin-C and improvement in metabolic status

Administration of estrogens to acromegalic patients has been shown to reduce the serum concentrations of bioassayable somatomedin and to cause improvement in clinical status. These effects appear not to result from an effect on the secretion of growth hormone since growth hormone concentrations are not consistently reduced. Using a sensitive radioimmunoassay for somatomedin-C, we have assessed the relationship between the estrogen-induced reduction of somatomedin-C and changes in several indices of disease activity in five acromegalic patients. Statistically significant reductions in serum somatomedin-C (p < 0.02), urinary hydroxyproline (p < 0.05) and the phosphate clearance ratio (p < 0.01) occurred within three days of the institution of treatment with 1 mg ethynyl estradiol daily. Unlike the consistent reduction in serum somatomedin-C erratic changes in growth hormone were observed. The decline in serum somatomedin-C was not due to an estrogen-induced increase in somatomedin-binding proteins since total serum somatomedin-C concentrations measured after treatment of serum with acid also were reduced by estrogen therapy, and the magnitude of this reduction was equivalent to that observed in untreated serum. The study indicates that the reduction of immunoreactive somatomedin-C correlates with estrogen-induced improvement in the metabolic activity of acromegalic patients and suggests that measurement of somatomedin-C may be useful in monitoring the effects of other drugs on this disease.

High Incidence of Cortical Atrophy of the Cerebral and Cerebellar Hemispheres in Cushing's Disease

Abstract One of the most striking generalized metabolic changes in Cushings disease is catabolism of protein, which results in protein depletion. The resultant osteoporosis, muscle wasting, skin atrophy, and fragility of the blood vessels have been recognized. The present study of 31 cases also shows a high degree of cerebral and cerebellar cortical atrophy in this disease.

Stereotactic Bragg Peak Proton Beam Therapy

Stereotactic Bragg peak proton beam therapy has been performed in more than 2,000 procedures during the past 25 years at the Harvard Cyclotron Unit. This technique was developed as particle beam surgery, in which the terminal energy peak of protons (Bragg peak) is directed to an intracranial target by the stereotactic method. Proton beams are not electromagnetic radiation but share with it the ability to induce ionization in biologic systems. There is no exit dose of radiation beyond the target. The dose (rad) of a single beam is two to four times greater than the path dose at the Bragg peak [6]. The Bragg peak of the proton beam is biologically more effective than are the plateau portion of the proton beam, cobalt-60 rays, or roentgen rays at the same physical dose [7, 13]. If a number of such beams are converged upon a brain target, the dose within the target may be many times greater than the dose along any path. For example, if 12 proton beams from different directions are focused upon a pituitary tumor, the dose within the tumor is more than 25 times as great as any path dose.

Arteriovenous malformation hemodynamics: a transcranial Doppler study.

Congenital arteriovenous malformation (AVM) of the brain represents a defect in capillary development resulting in a high flow fistula between arterial and venous systems. In this study, AVM hemodynamics were related with clinical findings. Volume flow was calculated based on transcranial Doppler (TCD) and angiographic data. Forty patients admitted to the Massachusetts General Hospital for proton beam therapy (33 +/- 10 yr old; mean +/- SD) were studied. Four symptoms were considered: intracranial bleeding, progressive neurological deficit, seizures, and headache. Fourteen control subjects aged 30 +/- 7 years (mean +/- SD) were normal volunteers. Angiography with calibrated markers permitting magnification correction was available for all patients. Lateral and medial depth limits of the intracranial basal arteries in relation to the TCD temporal window were determined by TCD and angiogram with excellent correlation. Selected depth for data acquisition was determined independently in the angiogram and by TCD. The difference between the two techniques was less than 4 mm. Mean flow velocity, pulsatility index, and vessel diameter were studied. Flow volume was calculated from these data. Mean flow velocity, pulsatility index, vessel diameter, and flow volume were significantly different among AVM feeders, non-feeders, and control arteries. The non-feeding middle cerebral artery, anterior cerebral artery, and posterior cerebral artery flows were 254 +/- 13, 136 +/- 14, and 79 +/- 8 ml/min, respectively. Accordingly, the estimated cerebral flow volume was 938 ml/min. The feeding middle cerebral artery, anterior cerebral artery, and posterior cerebral artery flows were 552 +/- 47, 369 +/- 70, and 484 +/- 67 ml/min, respectively (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebellar venous angioma associated with angiographically occult brain stem vascular malformation. Report of two cases

We studied two patients with angiographically documented cerebellar venous angioma (malformation) and angiographically occult vascular malformation of the brain stem. One patient had recurrent hemorrhage in the pontine tegmentum. The second patient had recurrent hemorrhage in the midbrain. None had hemorrhage originating from the abnormal cerebellar venous channels. The more benign nature of angiographic venous malformations is supported by the cases we are presenting, as well as from a review of the literature, which includes an autopsy study of similar cases. The management of multiple vascular brain lesions is contingent on the verification of symptomatic pathological blood vessels. It is emphasized that angiographically occult vascular malformation could possibly exist in the vicinity of angiographic venous malformation when the patient with intracerebral hemorrhage, especially in the posterior fossa, was diagnosed as having venous malformation.

Tension pneumocephalus of the cranial subdural space: a case report.

A case of subdural tension pneumocephalus is presented. Computerized cranial tomography permitted rapid diagnosis including localization of the air, thus facilitating prompt treatment. Tension pneumocephalus should be considered in a patient with a cerebrospinal fluid drainage device who deteriorates after craniotomy.

Human carcinoma of the breast, in vitro: The effect of hormones. A preliminary report

Cortisol, estradiol‐17B, progesterone, testosterone, and human chorionic gonadotropin altered 3H‐thymidine uptake in tissue culture suspensions of human breast carcinoma in 10 of 20 tumors studied. In 6 patients where there was an opportunity to observe the clinical response to hormonal therapy, an apparent correlation was present between the in vitro data and clinical course. This correlation suggests that this in vitro assay may be useful in selecting patients for hormonal therapy.

Transposition of Target Information from the Magnetic Resonance and Computed Tomography Scan Images to Conventional X-Ray Stereotactic Space

A technique to apply reconstructed X-ray computed tomography (CT) and magnetic resonance imaging (MRI) for target determination in stereotactic Bragg peak proton beam therapy of intracranial lesions was developed. Twenty-one benign intracranial tumors and vascular abnormalities were managed using this technique. Clinical features of these lesions, as well as targeting problems associated with the MRI and CT image interpretation, are presented.