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M Halks-Miller

Publications and source records attributed to M Halks-Miller.

28 records · Page 2Linked to original sources

Tocopherol-phospholipid liposomes: maximum content and stability to serum proteins.

This study addresses two questions: 1) what is the maximum amount of tocopherol that can be contained in egg phosphatidylcholine liposomes, and 2) what is the stability of these vesicles in the presence of serum proteins? These liposomes, made with a French pressure cell, can contain no more than 33 mol% of tocopherol. Tocopherol changes liposomes in a manner similar to cholesterol, making them larger, less permeable to aqueous dyes and highly resistant to protein-induced disruption. The suppression of protein-induced disruption is more pronounced with tocopherol than with cholesterol, even at lower molar ratios. Thus, liposomes containing alpha tocopherol (15 to 30 mol%) may be useful for delivering physiological quantities of this vitamin to cells in culture or to tissue in vivo.

Animals↗

Correction of congenital hydrocephalus in utero II: Efficacy of in utero shunting.

To study the effect of in utero ventricular decompression of hydrocephalus on brain development and prognosis, and to evaluate the function and possible complications of different shunt designs, we created fetal hydrocephalus in 28 fetal lambs and 17 fetal monkeys by injecting kaolin into the cisterna magna during the third trimester. One fetal lamb had indwelling intracranial subdural and amniotic cavity pressure catheters placed to study serial changes in the relationship of intracranial pressure (ICP) and amniotic fluid pressure (AFP) from the time of injection until term. Twenty hydrocephalic fetal lambs underwent ventricular decompression--ventriculoamniotic (V-A), N = 10; ventriculo-right atrial (V-RA), N = 9; and ventriculo-pleural (V-PL), N = 1--21 to 25 days after the kaolin was injected; seven hydrocephalic fetuses were left unshunted as controls (CON). Eight fetal monkeys underwent V-A decompression 14 to 21 days after kaolin injection; nine were left unshunted as controls. All animals were delivered by cesarean section near term, assessed for viability and their brains examined grossly and microscopically. After kaolin injection in the fetal lamb, ICP (r = 0.94) and ICP minus AFP (r = 0.93) rose in a linear fashion, while AFP showed no trend (r = 0.22). All unshunted newborn lambs and monkeys had split sutures, dilated ventricles, and thinned cortical mantle. Most shunted lambs showed anatomic improvement with decreased head circumference, overriding sutures, normal-sized ventricles, and improved survival. However, histopathology revealed marked white matter destruction. In contrast, most shunted monkeys showed little anatomic improvement. Both shunted and unshunted monkey brains showed a severe inflammatory ventriculitis. In both lambs and monkeys, shunting was associated with a variety of complications including subdural hematoma, subdural hygroma, shunt infection, shunt occlusion, and improper shunt tip placement. In this experimental model, in utero decompression of obstructive hydrocephalus improves overall survival, improves gross ventriculomegaly, does not improve histopathologic brain damage, and is associated with significant complications. The choice of the optimal shunt design and the effect on postnatal neurologic function requires further study. This work emphasizes the need for continuing research in an animal model prior to human application.

Amniotic Fluid↗

Neuroepithelial cysts of the posterior fossa: pathogenesis and report of two cases.

We present two cases of simple neuroepithelial cyst--one at the cerebellopontine angle and the other in the pontine brain stem--in which a basement membrane was detected. The pathogenesis of these cysts, their diagnosis using computed tomography-metrizamide cisternography and nuclear magnetic resonance imaging, and their surgical treatment by fenestration and drainage are discussed.

Adult↗

Kaolin-induced congenital hydrocephalus in utero in fetal lambs and rhesus monkeys.

A model of congenital hydrocephalus in utero in fetal lambs and rhesus monkeys has been produced by the intracisternal injection of kaolin. Initial attempts to produce hydrocephalus using silicone oil were unrewarding. Hydrocephalus had developed by 2 weeks post-injection and could be followed by ultrasonography. The pathological findings were similar to those reported using kaolin in other species. Ventriculoamniotic shunting, when successful, was capable of partially reversing the deleterious effects of hydrocephalus. The major drawback of the present model is that hydrocephalus is produced during the second rather than the first trimester of pregnancy. However, kaolin produces mainly an obstructive hydrocephalus without other associated brain or systemic anomalies.

Animals↗

Correction of congenital hydrocephalus in utero I. The model: intracisternal kaolin produces hydrocephalus in fetal lambs and rhesus monkeys.

In the fetus with congenital hydrocephalus, obstruction to the flow of cerebrospinal fluid (CSF) results in ventricular dilation and neurologic impairment. Decompression of the obstructed ventricles before birth may ameliorate the damage and allow normal development to proceed. Although appealing, this pathophysiologic rationale has not been adequately tested because a satisfactory fetal model has not been available. We have developed a model of obstructive hydrocephalus in the fetal lamb and rhesus monkey by injecting kaolin into the cisterna magna through the posterior atlanto-occipital membrane early in the last trimester. Preliminary studies injecting silicone oil were unsuccessful. The development of fetal ventriculomegaly was followed using prenatal ultrasonography. Massive hydrocephalus developed in six sheep, three liveborn at term and three stillborn after premature vaginal delivery, and in 2 fetal rhesus monkeys. All treated animals had external signs of hydrocephalus with marked cranial enlargement. Neuropathologic examinations demonstrated fibrosis of the leptomeninges and subarachnoid spaces around the fourth ventricle. Dilation of the lateral and third ventricles resulted, with attenuation of the cerebral white matter. On histologic examination, the grey matter was relatively well preserved, while the white matter was severely attenuated. This model mimics the clinical and pathologic picture seen in human infants and should allow us to study the pathophysiology of congenital obstructive hydrocephalus and the efficacy and feasibility of its correction in utero.

Animals↗

Vitamin E-enriched lipoproteins increase longevity of neurons in vitro.

Vitamin E-enriched human lipoprotein fractions were used to supplement the standard feeding medium of organotypic, reaggregate, fetal rat brain cultures. The neurons in control cultures, which were fed with Dulbecco's Modified Eagle's Medium containing 15% fetal calf serum, began to degenerate after 27 days. Those in test cultures, which were supplemented with 5-15 micrograms vitamin E/ml, survived until the end of the experiment (49 days). We conclude that differentiated, membrane-rich neurons and glia need a lipid-enriched and/or antioxidant-supplemented medium for prolonged survival in organotypic culture.

Animals↗

Rat C-6 glioma cells maintained in an organ culture system: a study of kinetic parameters.

Rat C-6 glioma cells were grown on a sponge foam matrix in an organ culture system and the cell cycle parameters, including the growth fraction (GF), were assessed after autoradiography. The zones of growth consisted of a compact upper layer (UL) at the gaseous interface, a central necrotic layer and a deeper lower layer (LL) which invaded the matrix. The fraction of continuously labeled mitoses (FCLM) was similar in both the UL and LL cells. The derivatives of the FCLM curves obtained in three experiments gave an average modal TG2 of 5 hr. A mathematical model relating GF, TG2, TC and labeling index as a function of time, LI(t), was devised for cells in a steady state exposed continuously to tritiated thymidine and was applied to data obtained from UL cells. A mean GF of 9% (range: 8-10%) and a mean cell cycle time (TC') of 27 hr (range: 13-47 hr) were obtained. The mean TS was calculated to be 11 hr (range: 8-16 hr) by the method of grain counts per mitotic figure or grain index (GI). Knowledge of TS permitted alternative calculation of the cell cycle time from the equation Ts/TC = LI(0)/GF:this gave a mean cell cycle time (TC") of 29 hr (range: 20-45hr). Except for the GF, the cell kinetics were comparable to those of the same cell line grown in monolayer culture. The GF in the in vitro system described is in the lower range reported in some human malignant gliomas in vivo.

Animals↗

Granulomatous amebic encephalitis presenting as a cerebral mass lesion.

Clinical and brain biopsy or autopsy findings in six patients with Granulomatous Amebic Encephalitis (GAE) due to acanthamoeba sp. were characterized by focal neurological symptoms, increased intracranial pressure, and focal neuroradiological findings. Craniotomies were performed because of the diagnostic possibility of a mass lesion such as a brain tumor or abscess. In four patients, frozen sections demonstrated free-living amebas. GAE may present as an acute or subacute intracerebral mass lesion with signs and symptoms of focal brain disease and should be differentiated from viral, bacterial, fungal, and other protozoal encephalitides.

Adult↗