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Biomedical subjects

M Dubach

Publications and source records attributed to M Dubach.

At least 19 recordsLinked to original sources
PubMed1998

Extended local access fibers: adjustable treatment of deep sites in the brain.

We describe a minimally invasive method for administering diffusible substances to computer-targeted regions of the primate brain. Treatments enter the brain by diffusion or under pressure from the portion of a curvilinear implant that lies within the region of interest. During the implantation surgery, a guide-tube cannula is passed through a cranial burr-hole and concentric, telescoping needles are extended from the cannula in sequence to trace a pre-planned course through brain tissue. After the leading end of the longest needle emerges through another burr-hole, the surgeon fastens a hollow dialysis fiber to its tip and draws the fiber into the brain by retracting the telescoping device in an orderly sequence. The surgery affects brain tissue only along the course of the fiber, causing about the same acute damage as the stereotactic introduction of an ordinary straight needle. The 'extended local access fiber' is relatively soft, flexible, and biocompatible. It remains permanently in the brain, with its semipermeable portion lodged in the target region. Leading and trailing portions are accessible from outside the brain. Experiments indicate a broad range of possible trajectories and confirm that substances delivered by access fiber can have physiological effects even 10 weeks after implantation.

Animals↗
PubMed1993

Effects of acute and chronic alprazolam treatment on cerebral blood flow, memory, sedation, and plasma catecholamines.

The effects of 0.014 mg/kg intravenous alprazolam administration on cerebral blood flow (CBF), memory, sedation, and plasma norepinephrine and epinephrine were determined in eight healthy males at baseline levels and following 1 week of daily oral alprazolam treatment. At baseline, intravenous alprazolam administration caused acute reductions in whole-brain CBF (25% to 30% decrease), memory, plasma epinephrine, and self-rated alertness. Following 1 week of alprazolam treatment, tolerance developed to the acute effects of intravenous alprazolam on CBF, memory, and plasma epinephrine. There were no consistent regional neuroanatomic differences in the CBF effects of acute alprazolam, or in the development of tolerance to these effects, and no correlations between the various measures of acute alprazolam effects on either test day.

Administration, Oral↗
PubMed1991

Adrenal medullary "ribbon" grafts in non-human primates: transplant method.

A novel stereotaxic method permits the transplantation of autologous adrenal medullary tissue into the brain parenchyma in longtailed macaques. Long, narrow "ribbons" of intact medullary tissue are drawn into a 19 gauge needle by suction and deposited in the caudate, putamen or substantia nigra without collapsing their linear conformation. Methods of dissection, preparation of medullary ribbons, stereotaxic insertion, and chronic intracerebroventricular treatment are described in detail. The ribbon method consistently yields a large amount of viable adrenal tissue after the 4-8 week survival times tested. Although further development is necessary before this method can be applied in humans, the results suggest that autologous adrenal tissue may be viable when transplanted in human parkinsonian patients according to these methods.

Adrenal Medulla↗
PubMed1991

Distribution of intracerebrally injected dopamine as studied by a punch-scintillation modeling technique.

Three-dimensional distribution gradients of intracerebrally injected tritiated dopamine were calculated on the basis of concentrations in multiple punch-samples from sequential sections of Macaca fascicularis brain tissue. The monkey was pretreated systemically with a monoamine oxidase inhibitor to retard elimination. Gradients were best fit by cubic exponential equations relating concentration to distance from the center of the site. The concentration at the center, total amount of label, and total extent of the site injected just before perfusion were consistent with initial distribution in the extracellular space, if the volume fraction of the latter is estimated at 20%. The extent of distribution was distinctly greater in the mediolateral and dorsoventral dimensions than in the anteroposterior dimension. The total amount of label near the site decreased rapidly in the first few minutes after injection, then much more slowly, reaching about 30% of the injected amount after 2 h. Its distribution within the site changed steadily, the outer boundary gradually expanding and the peak at the center gradually decreasing. This pattern was consistent with an initial rapid dispersion by injection pressure and an initial loss of tritiated dopamine due to disruption of the blood-brain barrier at the center of the site, followed by a steady expansion of the site driven by diffusion and bulk flow.

Animals↗
PubMed1991

Accurate stereotactic injection by radially curved injection needles.

A method has been developed for planning, constructing, and inserting radially curved injection needles for stereotactic surgery in primates. The stereotactic coordinates of the top of a guide tube and the targeted site, together with sagittal and coronal projections of the slant of the guide tube, are provided for the computer, which calculates the length, curvature, and rotational angle at which a curved injector should be inserted through the guide tube to reach the site. Development of the method included a test surgery in which curved injectors were lowered through one set of guide tubes and straight injectors through another set, targeted on the same points in the brain. Formulas used by the programs are presented, and the source code for the software is available on request.

Algorithms↗
PubMed1990

Extensive survival of chromaffin cells in adrenal medulla "ribbon" grafts in the monkey neostriatum.

Experimental neurosurgical implantation of adrenal medulla tissue has been performed as a treatment for Parkinson's disease at several medical centers around the world, and similar techniques have been applied in a small number of nonhuman primates. None of these efforts to date has resulted in histological evidence of significant graft survival, and behavioral improvement in patients has been modest at best. The present series of experiments, however, has led to a novel and effective technique for stereotaxic implantation of long, narrow "ribbons" of autologous adrenal tissue in the monkey caudate and putamen nuclei. The survival and enzymatic activity of large portions of intact grafted ribbons have been demonstrated by tyrosine hydroxylase immunohistochemistry. Efforts based on other grafting techniques resulted in poor or mediocre survival, reminiscent of previously published results. Successful grafts, on the contrary, were morphologically similar to intact adrenal medulla tissue, except that neuronal processes were observed emanating from some of the transplanted cells. The success of the present technique, which minimally distorts or traumatizes adrenal and brain tissue, may be due primarily to the rapid establishment of a blood supply by anastomosis with host vessels. In most monkeys, nerve growth factor was also administered to the lateral ventricle for the duration of the graft, but excellent results were also achieved in the monkey that did not receive such treatment. We conclude that adrenal grafts made by the present technique can survive and function in primates.

Adrenal Medulla↗
PubMed1988

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian syndrome in Macaca fascicularis: which midbrain dopaminergic neurons are lost?

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces, in both human and non-human primates, a syndrome very similar to idiopathic Parkinson's disease. The syndrome is associated with degeneration of the dopamine-containing neurons in the substantia nigra, many of which project to the neostriatum. The purpose of the present study was to quantify the regional distribution of midbrain dopamine neurons remaining after MPTP administration to the monkey (Macaca fascicularis) and to develop alternative procedures for maintaining the normal nutrition in MPTP-treated animals. Three monkeys were treated with MPTP and three served as controls. Representative sections were examined from rostral to caudal through the midbrain dopamine cell nuclei and the location of every tyrosine hydroxylase-containing cell was entered into a computer. Midbrain dopamine neuronal cell loss ranged from 36-78%, being most extensive in the two monkeys which exhibited the most severe parkinsonian syndrome. The greatest cell loss (46-93%) occurred in the substantia nigra pars compacta, or nucleus A9, and the loss was primarily in the ventral portion of the nucleus. Contrary to most previous reports, however, there was also a loss of cells in the ventral tegmental area (28-57%) and ventral reticular formation (33-87%), corresponding to nuclei A10 and A8, respectively. Since neuroanatomical tracing studies have shown that the dorsal and lateral portions of the striatum (areas showing the greatest dopamine depletion after MPTP) receive input from cells in the ventral A9 and from cells in the A8 and A10 areas, the present data suggest that MPTP preferentially destroys dopamine cells that project to the striatum (i.e. the mesostriatal cells).

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Primate neostriatal neurons containing tyrosine hydroxylase: immunohistochemical evidence.

We have detected, in monkey caudate nucleus and putamen, neuronal cell bodies containing tyrosine hydroxylase-like immunoreactivity, as revealed by peroxidase-antiperoxidase immunohistochemistry. Many of these cells are distributed in an outer rim of 1-2 mm throughout the anterior-posterior extent of the neostriatum near its borders with the corona radiata; others are embedded in the adjacent white matter, especially near the ventral putamen and nucleus accumbens. Light and electron microscopy indicate that they are small (8-12 micron), bipolar cells with large nuclei. Such neostriatal neurons, containing tyrosine hydroxylase-like immunoreactivity, number in the tens of thousands.

Animals↗
PubMed1981

Quantitative analysis of the respiratory system of the house sparrow, budgerigar and violet-eared hummingbird.

In the house sparrow, the budgerigar and the violet-eared hummingbird the volumes of the lungs and air sacs are estimated from silicone casts. The quantitative composition of the lungs and of their compartments are measured on lung slices, the relative volumes of the parabronchi on histological sections, and the volume composition of the blood-air capillary network of the parabronchi on electron micrographs. On electron micrographs the exchange surface and the thickness of the air-blood diffusion barrier are also measured. From these data the morphological membrane diffusion capacity is calculated and related to several organ weights. The volume of the lungs and air sacs makes up 14-22% of the total body volume, the lungs only 2.3-2.9%. The exchange surface varies from 61 cm2/g (budgerigar) over 70 cm2/g (house sparrow) to 99 cm2/g (violet-eared hummingbird). The very thin barrier in these small birds results in a membrane diffusion capacity of 0.122 in budgerigars up to 0.271 ml O2/mm Hg . min . g in violet-eared hummingbirds. The various parameters are compared with those of corresponding mammals, and the quantitative advantages of the avian respiratory system are discussed.

Animals↗
PubMedDate not supplied

Viable adrenal medullary transplants in non-human primates: increasing the number of grafts.

The robust survival of stereotaxic adrenal medullary autografts in monkey brain parenchyma depends heavily on technique. One aspect of technique critical for clinical applications of CNS grafting is the problem of spreading treatment effects throughout large regions in a primate brain. Stereotaxic placement of a large number of grafts, which would address this problem, would require that later grafts retain the capacity for viability over a long period of time during the surgery, while earlier grafts are being made. In the present experiments involving 12 longtailed macaques (Macaca fascicularis), some grafts remained in medium 2.5 h before being transplanted, without apparent loss of viability. A clinically sufficient distribution of graft tissue would also require a large number of separate grafts to be derived from one adrenal medulla. One method for subdividing the gland might be to cut it into numerous very small pieces, but various dicing techniques described in this report have yielded little viable graft tissue. On the other hand, the number of ribbon grafts of the original dimensions available from a single gland is rather small; adrenal ribbons of the original dimensions were therefore further dissected. Half-length and half-width ribbons were successful, but less so than full-size ribbons in terms of proportionate viability. An assay of behavioral effectiveness, applied to all subjects described here, is presented in a separate contribution.

Adrenal Medulla↗