Isolated cerebral intraaxial varix.

A case of isolated parenchymal venous varix not seen on angiography is reported. CT demonstrated a well-defined cystic lesion with peripheral enhancement deep within the left temporal lobe. MR demonstrated a high-signal-intensity lesion with hemosiderin rim.

Effect of thiols on micronucleus frequency in gamma-irradiated mammalian cells.

The effects of the thiols cysteamine, WR-1065, and WR-255591 on radiation-induced micronucleus (MN) frequency and cell killing were compared in cultured Chinese hamster ovary cells. MN were measured using the cytochalasin B assay of Fenech and Morley (1985), which minimizes the effect of cytokinetic perturbations on MN expression. The dose-response curves for MN induction were curvilinear both for control cells at doses between 1.5 and 4.5 Gy and for thiol-treated cells at doses between 3 and 9 Gy. Protection against MN induction by each thiol was independent of radiation dose. Furthermore, there was a close correlation between the degree of modification of MN induction and cell survival by each thiol, i.e., the MN frequency closely predicted the survival level regardless of the presence of absence of the thiols. A similar predictive relationship has also been reported by us for cell survival and DNA double-strand break (DSB) induction in this cell line following treatment with these same thiols. Collectively, these data support the hypothesis that, for DNA-repair-proficient mammalian cells treated with radiomodifying agents that do not alter DNA-repair processes, MN and DSB induction are predictive of the level of radiation lethality and of each other.

In vivo biological effects of stereotactic radiosurgery: a primate model.

Single-fraction, closed skull, small-volume irradiation (radiosurgery) of intact intracranial structures requires accurate knowledge of radiation tolerance. We have developed a baboon model to assess the in vivo destructive radiobiological effects of stereotactic radiosurgery. Three baboons received a single-fraction, 150-Gy lesion of the caudate nucleus, the thalamus, or the pons using the 8-mm diameter collimator of the gamma unit. Serial standard neurodiagnostic tests (neurological examination, computed tomographic scan, magnetic resonance imaging, stable xenon-enhanced computed tomographic scan of cerebral blood flow, somatosensory and brain stem evoked potentials, and myelin basic protein levels of cerebrospinal fluid) were compared with preoperative studies. Magnetic resonance imaging revealed the development of a lesion at the target site between 45 and 60 days after irradiation. Deterioration of the brain stem evoked potentials preceded imaging changes when the lesion encroached on auditory pathways. Myelin basic protein levels increased subsequent to imaging changes. Postmortem neuropathological examination confirmed a well-demarcated radionecrosis of the target volume. The baboon model appears to be an excellent method to study the in vivo biological effects of radiosurgery.

Comparative effect of the thiols dithiothreitol, cysteamine and WR-151326 on survival and on the induction of DNA damage in cultured Chinese hamster ovary cells exposed to gamma-radiation.

We compared the ability of three thiols--dithiothreitol (DTT), cysteamine and WR-151326--to protect aerated Chinese hamster ovary cells from the lethal and DNA-damaging effects of gamma-radiation. These results were compared with earlier measurements for WR-1065 and WR-255591. The time-course and the concentration dependence of protection against cell killing was determined after 10 Gy of gamma-rays. The aminothiols cysteamine and WR-151326 protected at much lower extracellular concentrations than the simple thiol DTT; however, there was no clear difference between the behaviour of cysteamine, WR-151326, WR-1065 and WR-255591 in this respect. Protection by DTT and cysteamine was complete within 1 min, whereas for WR-151326, WR-1065 and WR-255591 about 30 min was required before protection began to reach a plateau. Based on these data, complete radiation survival curves were generated for each thiol and protection factors calculated. Effects on the induction of DNA single-strand breaks (ssb) and double-strand breaks (dsb) by gamma-rays were measured using alkaline (pH 12.1) and neutral (pH 7.0 and 9.6) elution, respectively. All three thiols protected against ssb induction, although to a significantly lower extent than against cell killing measured under identical conditions. Each thiol also protected against dsb induction. After high radiation doses the protection factors for dsb induction were also less than the protection factors for cell survival; however, when dsb were assayed using the low-dose replicate plating neutral elution method, the relative effect of each thiol on cell survival and on dsb induction appeared to be equivalent. The hierarchy of protection against both ssb and dsb induction (based on the extracellular thiol concentration required to produce a given degree of protection) was similar to that for cell survival, i.e., WR-151326 congruent to cysteamine less than DTT.

Operative treatment of intracranial epidermoid cysts and cholesterol granulomas: report of 21 cases.

Thirteen patients had operations to remove intracranial epidermoid cysts, and long-term follow-up was obtained. Total or nearly total tumor and capsule removal was accomplished in 7 patients during the initial operation. This group required no additional operations. The other 6 underwent subtotal tumor removal and required multiple operations for symptomatic tumor recurrence. This latter group had a poorer neurological outcome. We conclude that initial total or near-total tumor resection is highly desirable in treating intracranial epidermoid cysts, particularly in physiologically young individuals. Five patients were followed after operations to remove pure cholesterol granulomas of the petroclival bone, and 3 additional patients were followed after operations to remove tumors with combined histopathological features of both an epidermoid cyst and cholesterol granuloma. Four patients with some component of a cholesterol granuloma had concurrent middle ear infections, and 4 did not. Intracranial subtotal excision and drainage of these lesions was the initial operative management in 7 patients, 5 of whom have required multiple operations for symptomatic tumor recurrence. Therefore, we conclude that subtotal excisional procedures for tumors with histopathological features of cholesterol granulomas are not usually successful in establishing long-term cures. Total excision, as recommended for epidermoid cysts, tumors frequently confused with cholesterol granulomas when occupying the petroclival region, may be warranted for these tumors as well. We postulate that when a congenital epidermoid cyst occurs in the petroclival bone, it may incite a local inflammatory reaction, producing lesions which have the histological features of both epidermoid cysts and cholesterol granulomas.

Generalized seizures following myelography with iohexol (Omnipaque).

A case of generalized seizures following lumbar myelogram with iohexol (Omnipaque) contrast agent is reported. This complication, occurring in a patient without known risk factors for developing epilepsy, is the first of its kind.

Protection by WR-3689 against gamma-ray-induced intestinal damage: comparative effect on clonogenic cell survival, mouse survival, and DNA damage.

The aminophosphorothioate WR-3689 was characterized for its ability to protect mouse jejunal cells in vivo from single doses of X or gamma radiation. First, the effect of the drug on the survival of jejunal stem cells was examined using a clonogenic end point, the crypt microcolony assay. When WR-3689 was administered 30 min prior to whole-body irradiation, the number of surviving crypt cells was markedly increased at all doses of the drug, although protection began to level out at doses larger than 600 mg/kg. Protection was maximal when the drug was given 30 min before whole-body irradiation and declined rapidly with both shorter and longer intervals. Protection factors (PFs) were obtained by measuring survival curves for clonogenic crypt cells as a function of radiation dose; WR-3689 given 30 min before whole-body irradiation protected jejunum in the microcolony assay with a PF of 1.26 +/- 0.02, 1.50 +/- 0.10, and 1.65 +/- 0.10 at doses of 200, 400, and 800 mg/kg, respectively. Next, the effect of WR-3689 on the survival of jejunal stem cells was determined by assaying the survival of mice given X-ray doses to the whole abdomen in the range leading to death from the gastrointestinal syndrome. The PFs based on the LD50 values for 11-day survival were 1.31 +/- 0.05 (200 mg/kg) and 1.48 +/- 0.05 (400 mg/kg). Crypt-cell survival and animal survival were thus modified to a similar extent by this agent. Finally, the effect of WR-3689 on the induction of DNA single-strand breaks (SSBs) in jejunal cells was measured using an adaptation of the alkaline elution methodology. In mice treated with WR-3689 (400 or 800 mg/kg) 30 min prior to whole-body irradiation with 10 Gy there was no significant reduction in the number of DNA SSBs induced either in samples of the jejunum or in the cycling crypt cells, providing further evidence that there is no simple relationship between the modification of DNA SSBs and the survival of jejunal stem cells.

Gamma knife radiosurgery for intracranial arteriovenous malformations in childhood and adolescence.

Eighteen children or adolescents with intracranial arteriovenous malformations (AVM) underwent stereotactic radiosurgery using the first North American gamma knife. This closed-skull, single-treatment therapy, utilizing 201 ionizing beams of gamma-irradiation, was used as an alternative to microsurgical removal in these selected patients (aged 34 months to 18 years, mean 12.3 years) beginning in August 1987. No significant perioperative morbidity occurred, and no patient rebled or died in the follow-up interval ranging between 7 and 19 months. Computed tomography (CT) and magnetic resonance imaging (MRI) were used to monitor the response to treatment and to determine when postoperative angiography was indicated. Of seven AVMs examined with cerebral angiography 1 year after treatment, three were completely obliterated; three others were significantly smaller, and their complete obliteration is anticipated by 2 years after treatment. Follow-up CT or MRI confirmed attenuation or signal changes suggestive of edema surrounding the treatment volume in 3 patients; 1 had transient worsening of a preexisting neurological deficit. Although a more long-term perspective is still required for this new technology now available in the United States, we believe that gamma knife stereotactic radiosurgery is a safe and effective method to obliterate AVM deemed too risky for microsurgical removal.

Radioprotection of cultured Chinese hamster ovary cells by WR-255591.

We examined the radioprotective effect of the aminothiol WR-255591 and its phosphorothioate derivative WR-3689 on aerated cultured Chinese hamster ovary cells. At concentrations up to 10 mmol dm-3, WR-3689 afforded little protection from the lethal effects of gamma-radiation. The free thiol WR-255591, on the other hand, efficiently protected these cells, giving a protection factor (PF) for cell survival of 2.3 at a concentration of 6 mmol dm-3. The effects of WR-255591 on the induction and rejoining of gamma-ray-induced DNA single-strand breaks (ssb) and double-strand breaks (dsb) were measured using alkaline (pH 12.1) and neutral (pH 7.0 or 9.6) elution, respectively. PFs calculated from these data were compared with the PFs measured for cell survival. WR-255591 (6 mmol dm-3) protected against the induction of both DNA ssb and dsb; however, the magnitude of the modification of both ssb (PF of 1.23) and dsb (PF of 1.83 at pH 7.0 and 1.70 at pH 9.6) was less than that for cell survival (PF of 2.3) measured under identical conditions (irradiation on ice). Treatment of cells with WR-255591 prior to irradiation retarded the subsequent rate of ssb rejoining but had no effect on dsb rejoining. Postirradiation treatment with the drug slightly retarded ssb rejoining but had no effect on cell survival. The observation of lower PFs for DNA strand breaks than for cell survival suggests that radioprotection by WR-255591 probably does not result from a uniform decrease in the induction of all types of DNA lesions. Rather, the drug may differentially protect against the induction of subclasses of DNA damage--which could also explain the effects on the kinetics of ssb rejoining--and/or enhance cellular recovery processes.

The ultrastructure of the thin limbs of Henle in Kidneys of the desert heteromyid (Perognathus penicillatus).

The thin limbs of both long- and short-looped nephrons in Perognathus kidneys were studied with transmission and scanning electron microscopy. The superficial nephrons have a short thin limb located in the vascular bundles of the outer medulla and are characterized by a simple, low-lying epithelium (0.4 +/- 0.1 mu thickness). In contrast, the first descending part of the thin limb of the majority of midcortical and juxtamedullary nephrons has a relatively thick epithelium (1.7 +/- 0.6 mu in thickness) with marked lateral and basal interdigitation and a dense surface covering of microvilli. The remaining part of the long descending thin limb is relatively simple with a low-lying epithelium (0.6 +/- 0.1 mu in thickness), decorated on its surface by sparse microplicae. The bend of the loop and the ascending limb are covered by a very simple low-lying epithelium (0.6 +/- 0.2 mu in thickness) with relatively little surface modification. The extreme urine-concentrating ability of Perognathus does not appear to be due to the development of a unique thin loop epithelium but rather to the extensive length of the inner and outer medulla.

Development of an assay for H2-receptor antagonists using isolated fat cells.

Fat cells were isolated by collagenase digestion of adipose tissue from male dogs. The cells were shown to be responsive to both histamine and norepinephrine in producing glycerol, a marker for lipolysis. The histamine-stimulated response was shown to be mediated by H2-receptors because it was inhibited by the H2-receptor antagonists metiamide and cimetidine, but not by H1 blockers such as tripelennamine, or by other agents such as propranolol. Conversely, norepinephrine-stimulated lipolysis was inhibited by propranolol but not by metiamide. The KD estimated for cimetidine and metiamide was approximately 10(-6) M, which compares favorably with that observed in other H2-receptor systems. The relative potency of various histamine H2-receptor agonists in this system was comparable to that seen in other H2-receptor systems. This assay has the advantage of utilizing a homogeneous cell preparation and is not complicated by tachyphylaxis. The dogs which are the source of the adipose tissue can potentially be used for other studies after a suitable recovery period. This system appears useful in screening novel compounds for H2-receptor antagonist or agonist activity.

Morphological study of the desert heteromyid kidney with emphasis on the genus Perognathus.

The renal morphology of three species of desert dwelling Perognathus rodents were compared to Dipodomys and two species of sympatric cricetid rodents. Perognathus has a highly adapted unipolar kidney capable of urine concentration up to 7,500 mOsm/KgH2O. Two major modifications were observed in these kidneys. (1) There is elongation of both the inner and outer medulla. When the thickness of the regions in P. penicillatus are factored by kidney weight it is found that the outer medulla is 3.8 and the inner medulla is 2.2 times greater in length than the extensively studied Dipodomys merriami. (2) There is great variance in glomerular size with approximately 20% of the glomeruli being very large and located in the juxta medullary region. These glomeruli are 1.5--1.6 times greater in diameter than the more numerous superficial glomeruli. These structural modifications are quantitated and the functional implications are discussed particularly in relation to urine concentrating ability in these desert inhabitants.