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G M Miller

Publications and source records attributed to G M Miller.

At least 19 recordsLinked to original sources
PubMed1995

Neuromodulation of transplanted gonadotropin-releasing hormone neurons in male and female hypogonadal mice with preoptic area brain grafts.

Implantation of normal preoptic area (POA) tissue into the third ventricle of adult hypogonadal (HPG) mice provides a source of GnRH neurons that innervate the host median eminence and stimulate reproductive development in the sterile mutants. To further evaluate graft-host integration, the effects of N-methyl-D,L-aspartic acid (NMA) and opiate antagonists on LH secretion in HPG mice with POA transplants (HPG/POA) were tested. NMA challenges significantly stimulated LH secretion in 10 of 11 HPG/POA females. Only 5 of 12 HPG/POA males responded to the same treatment. Administration of the opiate antagonists naloxone or naloxone methiodide was ineffective in stimulating LH release in any mice, but opiate antagonist pretreatment significantly potentiated the LH secretory response to NMA in female, but not male, HPG/POA mice. A potential anatomical substrate for this facilitation may be the beta-endorphin-immunoreactive innervation of the POA grafts in all HPG/POA brains examined. beta-Endorphin fibers were also present in the median eminence in the vicinity of GnRH outgrowth from the grafts. However, similar innervation patterns in HPG/POA males that did not respond to opioid antagonism suggests that this is not sufficient. We tested whether the sex difference in HPG/POA responsivity to neuromodulation is related to the steroid milieu in the hosts. 17 beta-Estradiol (E2) treatment facilitated the LH secretory response of male HPG/POA to NMA challenges whether animals were castrated and given an E2 capsule prior to graft implantation or one week before testing two months after graft surgery. Intact or vehicle (sesame oil)-treated, castrated HPG/POA males rarely responded to NMA challenges, yet graft-derived GnRH innervation of the hosts' median eminence was comparable in all treatment groups. GnRH challenge testing indicated that pituitary sensitivity of the HPG/POA males was not significantly altered by E2 treatment, suggesting that estrogen acted centrally. These results indicate that the activity of grafted GnRH neurons may be modulated by endogenous opioids of host origin as well as by the hormonal milieu.

Animals↗
PubMed1995

Somatostatin receptor subtype gene expression in pituitary adenomas.

Somatostatin (SRIF) exerts its diverse biological effects through a family of membrane receptors. In addition to inhibiting GH secretion, SRIF has antiproliferative effects and has been used clinically in the treatment of pituitary tumors. SRIF receptor (SSTR) expression has recently been identified in pituitary adenomas, and it is unknown whether differential expression of SSTR subtypes predicts clinical responses to SRIF analogs. We therefore determined which SSTR subtype messenger RNAs (mRNAs) are expressed in pituitary adenoma phenotypes and in normal human pituitary tissue using reverse transcriptase-polymerase chain reaction and tested whether expression of specific SSTR subtype mRNA is necessary for SRIF inhibition of GH secretion in human somatotroph adenomas in vitro. Expression of SSTR subtypes 1, 2, and 5 mRNA was identified in all pituitary adenoma types and normal pituitary tissue. In contrast, SSTR3 mRNA was detected in only one somatotroph adenoma as well as in control insulinoma tissue, a tissue known to express SSTR3 mRNA, and was not detected in normal pituitary tissue. SSTR4 mRNA was not detected in any human pituitary tissue. To determine whether specific SSTR subtype mRNA expression is required for SRIF inhibition of GH secretion, five somatotroph adenomas were treated with 10(-7) mol/L SRIF in vitro, and significant inhibition of GH release occurred in all adenomas. All five tumors expressed SSTR2 mRNA and SSTR5 mRNA, and three expressed SSTR1 mRNA. The absence of SSTR1 mRNA expression did not affect the ability of SRIF to suppress GH secretion. We conclude that: 1) human pituitary adenomas and normal pituitary express multiple SSTR gene transcripts; 2) SSTR5 mRNA, which has not been reported in other human endocrine tumor types, is expressed in neoplastic and normal pituitary tissue; and 3) SSTR2 mRNA, SSTR5 mRNA, and variable SSTR1 mRNA are expressed in GH-secreting tumors, which are responsive to SRIF in vitro. Further understanding of SSTR gene expression in pituitary adenomas will facilitate our understanding of the pathogenetic mechanisms of tumorigenesis and may provide a rationale for the use of specific SRIF analogs for clinical application.

Adenoma↗
PubMed1995

Meningeal biopsy in intracranial hypotension: meningeal enhancement on MRI.

Intracranial hypotension is a cause of diffuse enhancement of the pachymeninx with gadolinium, which often is associated with subdural fluid collections. We reviewed the results of meningeal biopsy in six patients with intracranial hypotension and diffuse pachymeningeal enhancement to correlate the MRI findings with histopathologic observations and to explain the abnormalities seen on MRI. Grossly, the dura mater was unremarkable in all patients, as were the leptomeninges, except for one patient with prolonged (18 months) intracranial hypotension in whom the arachnoid was thickened and opaque. Microscopically, the dura mater was entirely normal on its epidural aspect; however, a fairly thin zone of fibroblasts and thin-walled small blood vessels in an amorphous matrix was noted on the subdural aspect. In the patient with longstanding symptoms, diffuse benign arachnoidal cell proliferation was also noted, probably a reaction triggered by longstanding changes in the subdural area, as noted in the five other patients. There was no evidence of inflammation, infection, or metastatic neoplasia. These findings suggest that in intracranial hypotension, the dural-meningeal abnormalities probably represent reactive secondary phenomena, likely related to hydrostatic changes in the CSF, and not a primary meningeal process.

Aged↗
PubMed1995

Hemangioblastoma of the optic nerve: case report.

An optic nerve hemangioblastoma arising in the optic nerve of a patient with von Hippel-Lindau syndrome is reported. This represents the 10th published example of a hemangioblastoma arising at this site, the second description of the magnetic resonance imaging features of a hemangioblastoma at this location, and the second patient from whom an optic nerve hemangioblastoma has been removed with the goal of preserving the optic nerve as well as vision. A majority of these optic nerve hemangioblastomas have arisen in patients with von Hippel-Lindau syndrome. All patients experienced progressive loss of vision either to blindness or surgical intervention, although a vast majority of the lesions were sharply demarcated from the adjacent nerve and, thus, potentially resectable. Optic nerve hemangioblastomas are a rare cause of blindness but potentially preventable when treated with a conservative surgical approach aided by neuroimaging guidance. The recognition of discordance between the degree of vision loss and the extent or progression of a retinal hemangioblastoma may be an important clue to diagnosis in the patient with von Hippel-Lindau syndrome.

Adult↗
PubMed1995

Papillary craniopharyngioma: a clinicopathological study of 48 cases.

Two distinct clinicopathological variants of craniopharyngioma exist: the classic adamantinomatous type and a recently described papillary form that predominates in adults and reportedly behaves in a less aggressive manner. The present study describes the clinicopathological features of 48 patients with papillary craniopharyngioma treated at the Mayo Clinic between 1910 and 1994. An additional four tumors were found to have histological features of both adamantinomatous and papillary craniopharyngioma. Whereas adamantinomatous tumors typically occur in adolescent patients, the mean age of the 48 patients (23 males and 25 females) with papillary craniopharyngioma was 44.7 years (range 10 to 74 years). Presenting clinical features included visual impairment (84%), headache (68%), and pituitary insufficiency (anterior 42%; posterior 27%). Preoperative computerized tomography (CT) and magnetic resonance (MR) imaging in 17 patients typically revealed a noncalcified, partially cystic mass that enhanced peripherally and contained mural nodules (67%). Many (41%) of the lesions involved or extended into the third ventricle on imaging. At first surgery, gross total tumor removal was achieved in 17 patients (36%) and subtotal resection in 30 patients (64%) in whom tumor resection was attempted. Tumor recurrence was noted in two patients who underwent gross total removal. Tumor-free survival rates of 100% and 78% were obtained in patients who underwent gross total and subtotal resection at initial surgery, respectively. Postoperative radiation therapy was beneficial to patients having undergone a subtotal resection, with an increase in tumor-free survival from 26% to 86%. Aside from well-documented morphological distinctions, papillary craniopharyngiomas differ from adamantinomatous tumors in several important respects. These include the almost exclusive occurrence of papillary tumors in adulthood and their more uniform appearance on both CT and MR imaging. However, a preliminary analysis of our data suggests there are no significant differences between the two lesions with respect to resectability, efficacy of radiation therapy, and overall survival.

Adolescent↗
PubMed1995

Cervical disk prolapse.

OBJECTIVE: To correlate the findings on computed tomographic myelography (CTM) with surgically and pathologically proven prolapsed cervical disks, mention other pertinent cross-sectional imaging studies, and note the clinical relevance of certain CTM features. DESIGN: We retrospectively reviewed the medical and radiologic records of Mayo patients with suspected degenerative cervical disk disease during a 4-year period. MATERIAL AND METHODS: Between January 1986 and December 1989, 734 patients with possible cervical disk disease underwent assessment by CTM. An extruded disk was noted in 297 of these patients. In this study group, magnetic resonance (MR) imaging was also done in 28 patients and plain computed tomography was performed in 14, and we summarized those findings. RESULTS: Of the 297 study patients, 280 had a cervical radiculopathy and 17 had a myelopathy. CTM identified more than 90% of the extruded cervical disks. CTM could not distinguish between an osteophytic cartilaginous cap and a disk, and CTM could not identify the source of a cervical radiculopathy in 102 patients. Although only a few imaging studies other than CTM were performed, those modalities were less sensitive in the detection of prolapsed disks. CONCLUSION: Imaging of cervical disk prolapse continues to be difficult, and the results are not always specific. CTM is the most sensitive imaging examination, but the number of MR studies in the current series of patients was insufficient for a reasonable comparison between the two modalities.

Adult↗
PubMed1995

Cortical petechial hemorrhage, leukoencephalopathy, and subacute dementia associated with seizures due to cerebral amyloid angiopathy.

Although cerebral amyloid angiopathy is a well-known cause of cerebral lobar hemorrhage, subacute dementia, seizures, and acute encephalopathy without lobar hemorrhage are infrequently recognized as manifestations of this disease. In this report, we describe a case of cerebral amyloid angiopathy in a 74-year-old woman who had subacute progressive dementia and a superimposed rapid acute neurologic deterioration associated with seizures and the presence of cerebral edema on computed tomographic scans and leukoencephalopathy and cortical petechial hemorrhages on magnetic resonance imaging. A diagnosis of cerebral amyloid angiopathy in conjunction with small cortical infarcts and petechial hemorrhages was confirmed by antemortem biopsy. This clinical and radiologic picture is being increasingly recognized as characteristic of cerebral amyloid angiopathy.

Aged↗
PubMed1994

Cervical spondylotic stenosis and myelopathy: evaluation with computed tomographic myelography.

OBJECTIVE: To determine which components of cervical spondylosis are most frequently present in patients with myelopathy. DESIGN: We reviewed the findings in 93 patients who underwent surgical decompression for cervical spondylotic myelopathy between January 1986 and December 1989 at Mayo Clinic Rochester. MATERIAL AND METHODS: All 93 patients (72 men and 21 women) underwent computed tomographic (CT) myelography. In addition, magnetic resonance imaging scans were available in 25 patients, and plain CT scans were obtained in 2. RESULTS: A review of CT myelograms revealed that all neurocompressive intraspinal spondylotic changes were reflected in the shape of the spinal cord. Among the 93 patients with myelopathy, the configuration of the spinal cord could be categorized into primarily three dominant types: A (severe encroachment that compressed the cord into the shape of a banana; N = 40), B (moderate encroachment that produced less prominent compression; N = 23), and C (moderate bilateral uncovertebral spurs; N = 12). As a comparison group, 30 patients with similar spinal cord deformities but without progressive myelopathy were analyzed. Correlation of the two groups showed that myelopathy was present in up to 98% of patients with type A spinal cord, in 75% with type B, and in 71% with type C. The findings on magnetic resonance imaging were similar to those on CT myelography, but the bony spondylotic components were less readily seen. CONCLUSION: The precise pathophysiologic mechanism of myelopathy in spondylosis remains an enigma. Although the bulk of the data on our patients supports direct compression, we believe that the cause is multifactorial.

Adult↗
PubMed1994

Opioidergic modulation of N-methyl-D,L-aspartic-acid-stimulated LH release in young adult but not older male mice.

Among the neuromodulators of the GnRH neuronal system are the endogenous opioid peptides and the excitatory amino acids. Although the opioid antagonist naloxone (NAL) induces LH secretion in many species, there are no reports of an effect of NAL on LH release in mice. Our previous studies demonstrated that the excitatory amino acid analog N-methyl-D,L-aspartic acid (NMA) stimulates LH release in mice and suggested that NMA-induced LH release is mediated via afferents to GnRH neurons. In the current study, the role of the endogenous opioid system in the regulation of LH release in adult male mice was assessed by testing whether this system is a component of the NMA-stimulated LH response. NAL, its quaternary derivative NAL methiodide (which remains outside of the blood-brain barrier) and saline (SAL) were administered alone and in combination with NMA via intravenous catheters. Although neither opioid antagonist stimulated LH release when administered alone, each significantly potentiated the LH response to NMA in young adult (10- to 14-week-old) male mice (p < 0.01) but not in older (10- to 16-month-old) male mice. The equivalent action of the two ipioid blockers suggested an action outside of the blood-brain barrier. To determine whether opioid blockade altered pituitary sensitivity to GnRH, a dose response for exogenously administered GnRH was first determined, and low and high doses of GnRH were tested in combination with NAL or SAL. Neither treatment was effective in altering the LH response to GnRH, indicating that the action of the opioid antagonists was at a suprapituitary location. (ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

Sarcomas of calvarial bones: rare remote effect of radiation therapy for brain tumors.

After latent periods lasting from 7 to 23 years, sarcomas of the calvaria developed in four patients who had received radiation therapy for a brain tumor. There was no evidence of bony disease before radiation therapy, and the sarcoma (two fibrosarcomas and two osteosarcomas) developed in the field of radiation in all four patients. One of these four died during resection of the tumor, two survived for either 7 or 21 months after diagnosis of the sarcoma, and one was alive at 23 months after the clinical appearance of the sarcoma. The latter patient has had two resections and extensive chemotherapy. Distant metastases were not present in any of the patients. Sarcoma of the calvarial bones is a serious but rare remote effect of radiation therapy for brain tumors.

Adolescent↗
PubMed1994

Symptomatic glial cysts of the pineal gland.

Small asymptomatic cysts of the pineal gland represent a common incidental finding in adults undergoing computerized tomography or magnetic resonance (MR) imaging or at postmortem examination. In contrast, large symptomatic pineal cysts are rare, being limited to individual case reports or small series. The authors have reviewed 24 cases of large pineal cysts. The mean patient age at presentation was 28.7 years (range 15 to 46 years); 18 were female and six male. Presenting features in 20 symptomatic cases included: headache in 19; nausea and/or vomiting in seven; papilledema in five; visual disturbances in five (diplopia in three, "blurred vision" in two, and unilateral partial oculomotor nerve palsy in one); Parinaud's syndrome in two; hemiparesis in one; hemisensory aberration in one; and seizures in one. Four lesions were discovered incidentally. Magnetic resonance imaging typically demonstrated a 0.8- to 3.0-cm diameter mass (mean 1.7 cm) with homogeneous decreased signal intensity on T1-weighted images, increased signal intensity on T2-weighted images, and a distinct margin. Hydrocephalus was present in eight cases. The cysts were surgically excised via an infratentorial/supracerebellar approach (23 cases) or stereotactically biopsied (one case). Histological examination revealed a cyst wall 0.5 to 2.0 mm thick comprised of three layers: an outer fibrous layer, a middle layer of pineal parenchymal cells with variable calcification, and an inner layer of hypocellular glial tissue often exhibiting Rosenthal fibers and/or granular bodies. Evidence of prior hemorrhage, mild astrocytic degenerative atypia, and disorganization of pineal parenchyma were often present. Postoperative follow-up review in all 24 cases (range 3 months to 10 years) revealed no complications in 21, mild ocular movement deficit in one, gradually resolving Parinaud's syndrome in one, and radiographic evidence of a postoperative venous infarct of the superior cerebellum with ataxia of 1 week's duration in one. Of the patients referred for study, the cysts were most often initially misdiagnosed as a pineocytoma in eight and a pilocytic astrocytoma in three. Only two patients were correctly diagnosed as having pineal cysts. This stresses the importance of recognizing the histopathological spectrum of pineal cysts, as well as correlation with radiographic findings, if a correct diagnosis is to be attained.

Adolescent↗
PubMed1994

Benign glial cysts of the pineal gland: unusual imaging characteristics with histologic correlation.

PURPOSE: To describe the spectrum of MR and CT findings in clinically symptomatic pineal cysts and to determine whether there are certain diagnostic imaging features that allow one to distinguish a benign pineal cyst from other neoplasms of the pineal region. METHODS: MR and CT scans of 19 patients with clinically symptomatic pineal cysts were retrospectively reviewed. Age range was 15 to 46 years with a mean age of 28 years. There were five male and 14 female patients. RESULTS: Presenting features included headache (15 patients), diplopia (four), nausea and vomiting (four), papilledema (four), seizure (three), Parinaud syndrome (two), ataxia (one), and hemiparesis (one). All cysts were resected or biopsied to provide histopathologic confirmation of the diagnosis. Preoperative diagnoses included pineal neoplasm (14 of 19), pineal cyst (3 of 19), and dermoid cyst (2 of 19). The lesions ranged from 0.8 to 3.0 cm, with a mean diameter of 1.6 cm. Three cysts showed fluid/fluid levels consistent with hemorrhage. Slightly less than half (9 of 19) had evidence of hydrocephalus. The MR signal changes were variable but typically demonstrated low signal on T1-weighted images and high signal on T2-weighted images. More than half (7 of 12) demonstrated enhancement with gadolinium. Calcification of the cyst wall was observed in only four of nine patients who had CT studies but identified histologically in all cases. CONCLUSION: The MR appearance of benign pineal cysts is variable, ranging from that of an uncomplicated cystic mass to a mass associated with hemorrhage, enhancement, or hydrocephalus. This variability may make them indistinguishable from other pineal-region tumors.

Adolescent↗
PubMed1993

Cervical neural foraminal canal stenosis: computerized tomographic myelography diagnosis.

The surgical and computerized tomographic myelography (CTM) features of 134 stenotic foraminal canals were correlated retrospectively in 95 patients. The myelographic site of stenosis was the entrance to the foraminal canal in 70 cases (52%) and the canal itself in 37 (28%); the site was not identified definitively in 27 (20%). At the entrance to the foraminal canal, encroachment on the adjacent nerve root was by a cartilaginous cap in 10 cases (8%), a bony osteophyte in 17 (13%), a synovial cyst in one (1%), and a combination of a bony and cartilaginous osteophyte in 42 (31%). The diagnostic features of stenosis within the foraminal canal were more variable. Small bone spurs arising from the uncovertebral process encroached on the anterior aspect of the foramen in 29 instances (22%), accompanied in all cases by either a congenitally narrow canal (in 16) or a diffuse osteophytically narrowed canal (in 13); osteophytes arising from the superior facet in eight instances (6%) were larger and encroached on the posterior aspect of the foramen. Diagnosis on the basis of CTM is difficult because stenosis was readily evident as a bone spur in only 13% of cases, could not be distinguished from prolapsed disc in 39%, had to be differentiated from a congenitally narrow foraminal canal in 27%, and was frankly missed in 20% of the instances of stenosis.

Adult↗
PubMed1993

Intracranial parenchymal schwannoma. A clinicopathological and neuroimaging study of nine cases.

The clinical, radiological, and pathological features of nine cases of intracranial parenchymal schwannoma are described. The clinical course in four patients 23 years of age or younger mirrored the indolent nature of this neoplasm. Imaging studies included computerized tomography in eight patients and magnetic resonance imaging in three. The lesions were well demarcated with only mild surrounding edema. Five tumors were deep within the temporoparieto-occipital region, three were in the cerebellum, and one lay peripherally in the parietal lobe. Over two-thirds of the nine tumors were either cystic (five) or contained areas of cystic degeneration (two). One lesion was frankly hemorrhagic. A variety of imaging characteristics and contrast enhancement patterns were observed, including those of a cyst with a mural nodule and peripheral enhancement. Of the four solid neoplasms, two enhanced homogeneously while the other two demonstrated heterogeneous enhancement. Six tumors were resected totally. The follow-up period ranging from 2 months to 2 years has shown no recurrences. Microscopically, immunohistochemically, and ultrastructurally, the tumors were indistinguishable from peripheral schwannomas. A possible mechanism underlying the histogenesis of these rare lesions is discussed. The importance of recognizing this tumor is stressed, particularly in younger patients, given its benign nature, radiological resemblance to other tumors such as pilocytic astrocytoma, and favorable response to resection.

Adolescent↗
PubMed1992

Intrahypothalamic injection of a cell line secreting gonadotropin-releasing hormone results in cellular differentiation and reversal of hypogonadism in mutant mice.

GT1 is an immortalized cell line that synthesizes and secretes the neurohormone gonadotropin-releasing hormone (GnRH). We have placed these cells into the brains of adult mutant hypogonadal (hpg) mice, which lack a functional GnRH gene, to determine whether such cells could differentiate in situ and support gonadal development. Immunocytochemical detection of GnRH revealed that these cells migrated widely in the central nervous system and elaborated axonal processes which on rare occasion projected to the normal target, the median eminence. Using a battery of antibodies, we demonstrated that these cells could cleave the GnRH precursor and that the amidated decapeptide as well as other cleavage products were present. The presence of biologically active material and its appropriate secretion were further documented by gonadal growth in both males and females. The morphological differentiation of the GT1 cells correlated with the density of cells injected. Those remaining within the injection site and/or forming a tumor retained a simple, rounded or fibroblastic appearance. Those cells that migrated into the host away from such tumors assumed the simple fusiform shape of normal GnRH neurons with dendrites extending from one or both poles. When cell density was drastically reduced a much more complex dendritic arbor was elaborated. These data suggest that such cell lines can be useful in reversing genetic defects and in studying such processes as GnRH neuronal migration, axonal targeting, and cytological differentiation.

Animals↗