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Biomedical subjects

M H Weiss

Publications and source records attributed to M H Weiss.

At least 19 recordsLinked to original sources
PubMed2001

Approaches to the sellar and parasellar region: anatomic comparison of endonasal-transsphenoidal, sublabial-transsphenoidal, and transethmoidal approaches.

Various surgical approaches have been described for treating lesions which arise in the sellar region. The popular transnasal-transsphenoidal and transethmoidal-transsphenoidal approaches avoid the morbidity associated with transcranial operations while allowing enough exposure to successfully remove most lesions that arise in and around the sella. The goal of the present study was to accurately quantify the amount of exposure to the sellar and suprasellar region that the transethmoidal-transsphenoidal, endonasal-transphenoidal, and sublabial-transsphenoidal approaches provide. Each of the three approaches was performed on 14 formalin fixed heads with the aid of the operative microscope. The distances of relevant surgical landmarks, and the amount of exposure superior and anterior to the dorsum sella as well as the lateral exposure obtained through each of these approaches was carefully recorded. The mean distances were then used to calculate the volume of exposure offered by each approach. It was found that the sublabial-transsphenoidal approach afforded the greatest volume of exposure superior and anterior to the dorsum sella. The endonasal-transsphenoidal and the transethmoidal approaches were both found to offer less suprasellar volume exposure, with the transethmoidal approach offering the least. The authors believe the information obtained through this study illustrates some important anatomical relationships which can be used to advantage by the surgeon to tailor the most appropriate approach, depending upon the precise location of the lesion either within the sella or suprasellar region.

Brain Neoplasms↗
PubMed2001

The history and evolution of transsphenoidal surgery.

Initial attempts at transcranial approaches to the pituitary gland in the late 1800s and early 1900s resulted in a mortality rate that was generally considered prohibitive. Schloffer suggested the use of a transsphenoidal route as a safer, alternative approach to the sella turcica. He reported the first successful removal of a pituitary tumor via the transsphenoidal approach in 1906. His procedure underwent a number of modifications by interested surgeons, the culmination of which was A. E. Halstead's description in 1910 of a sublabial gingival incision for the initial stage of exposure. From 1910 to 1925, Cushing, combining a number of suggestions made by previous authors, refined the transsphenoidal approach and used it to operate on 231 pituitary tumors, with a mortality rate of 5.6%. As he developed increasing expertise with transcranial surgery, however, Cushing reduced his mortality rate to 4.5%. With the transcranial approach, he was able to verify suprasellar tumors and achieve better decompression of the optic apparatus, resulting in better recovery of vision and a lower recurrence rate. As a result he and most other neurosurgeons at the time abandoned the transnasal in favor of the transcranial approaches. Norman Dott, a visiting scholar who studied with Cushing in 1923, returned to Edinburgh, Scotland, and continued to use the transsphenoidal procedure while others pursued transcranial approaches. Dott introduced the procedure to Gerard Guiot, who published excellent results with the transsphenoidal approach and revived the interest of many physicians throughout Europe in the early 1960s. Jules Hardy, who used intraoperative fluoroscopy while learning the transsphenoidal approach from Guiot, then introduced the operating microscope to further refine the procedure; he thereby significantly improved its efficacy and decreased surgical morbidity. With the development of antibiotic drugs and modern microinstrumentation, the transsphenoidal approach became the preferred route for the removal of lesions that were confined to the sella turcica. The evolution of the transsphenoidal approaches and their current applications and modifications are discussed.

History, 19th Century↗
PubMed1999

Invasive pituitary adenomas: significance of proliferation parameters.

Although most pituitary adenomas behave in a purely benign fashion, microscopic invasion of the subjacent dura is very common, and clinically overt infiltration of the surrounding dura and bone is apparent at intraoperative inspection in about one third of cases. The factors governing invasive behavior remain unknown but are believed to be separate from those regulating cell proliferation. Histological features alone do not distinguish between benign, invasive, and malignant tumors of adenohypophyseal origin. Multiple attempts have been made to identify prognostic markers of aggressive behavior among these tumors. They include cytogenetic analysis of putative tumor suppressor genes or proto-oncogenes as well as immunohistochemical detection of cell-cycle specific antigens. At present, however, these analyses can neither distinguish the indolent pituitary adenoma from one that will pursue an invasive course, nor reliably predict the prognosis in individual patients.

Adenoma↗
PubMed1999

A functioning composite 'corticotroph' pituitary adenoma with interspersed adrenocortical cells.

We report the third case of a composite corticotroph pituitary adenoma with interspersed adrenocortical cells. The 16-year-old male patient presented with findings of delayed growth and pubertal arrest. In contrast to the previous two cases, this patient's tumor showed evidence of function as demonstrated by an elevated urinary cortisol level. Imaging studies revealed a sellar mass that was excised transsphenoidally. Histologic examination revealed a composite tumor composed of distinct populations of large and small cells. The small cell population was PAS-positive and immunohistochemically positive for adrenocorticotrophic hormone. The large cell population had abundant vacuolated cytoplasm, was negative for PAS and adrenocorticotrophic hormone, and stained positively for a panel of markers found in steroid-producing adrenocortical cells. Both populations showed evidence of proliferation as manifest by the presence of MIB-1 positive cells. Ultrastructural examination confirmed the presence of distinct populations of large adrenocortical cells and small corticotrophs, with intercellular junctions between the 2 cell types. The intimate relationship between the 2 cell populations and the activated appearance of the adrenocortical cells suggests the possibility of a paracrine relationship between the two cell types. The identification of 3 patients with sellar tumors demonstrating strikingly similar morphological and ultrastructural features, and all occurring in the second decade of life, suggests that this represents a distinct pathologic entity.

Adenoma↗
PubMed1999

Retroviral vector-mediated transfer and expression of human tissue plasminogen activator cDNA in bovine brain endothelial cells.

OBJECTIVES: Gene transfer of thrombolytic enzymes to vascular endothelial cells may influence the kinetics of intravascular thrombosis. This study defines the potential for gene transfer of tissue plasminogen activator (tPA) into bovine brain endothelial cells (BBEC). METHODS: The retroviral vectors derived from murine leukemia virus (MuLV) were used to transfer human tPA cDNA to BBEC. The tPA activity, tPA antigen and tPA inhibitor 1 (PAI-1) antigen were determined in the supernatant of transduced (BBEC/tPA) cell cultures by an immunoassay. RESULTS: The tPA antigen and enzymatic activity in cell culture supernatants of BBEC/tPA transduced cells were 75 ng/ml and 14 IU/ml after 4 days, that was 25 and 28-fold higher compared to the respective values in control cells. The PAI-1 antigen was not affected by tPA cDNA transfer. The Western blot assay of cell lysates confirmed that the majority of tPA in BBEC/tPA transduced cells was in the form of free tPA. While the maximal transduction efficiency of BBEC with an amphotropic MuLV vector was about 15%, a MuLV pseudotyped with vesicular stomatitis virus G glycoprotein envelope achieved high > 90% maximal transduction efficiency. CONCLUSIONS: The fibrinolytic activity of brain endothelial cells can be enhanced by transferring human tPA cDNA. These findings provide an initial step in implementation of future studies that investigate the use of this technology as an adjunctive treatment for cerebrovascular disease.

Animals↗
PubMed1999

Tissue plasminogen activator (tPA) deficiency exacerbates cerebrovascular fibrin deposition and brain injury in a murine stroke model: studies in tPA-deficient mice and wild-type mice on a matched genetic background.

Although the serine protease, tissue plasminogen activator (tPA), is approved by the US Food and Drug Administration for therapy to combat focal cerebral infarction, the basic concept of thrombolytic tPA therapy for stroke was challenged by recent studies that used genetically manipulated tPA-deficient (tPA-/-) mice, which suggested that tPA mediates ischemic neuronal damage. However, those studies were potentially flawed because the genotypes of tPA-/- and wild-type control mice were not entirely clear, and ischemic neuronal injury was evaluated in isolation of tPA effects on brain thrombosis. Using mice with appropriate genetic backgrounds and a middle cerebral artery occlusion stroke model with nonsiliconized thread, which does lead to microvascular thrombus formation, in the present study we determined the risk for cerebrovascular thrombosis and neuronal injury in tPA-/- and genetically matched tPA+/+ mice subjected to transient focal ischemia. Cerebrovascular fibrin deposition and the infarction volume were increased by 8.2- and 6. 7-fold in tPA-/- versus tPA+/+ mice, respectively, and these variables were correlated with reduced cerebral blood flow up to 58% (P<0.05) and impaired motor neurological score by 70% (P<0.05). Our findings indicate that tPA deficiency exacerbates ischemia-induced cerebrovascular thrombosis and that endogenous tPA protects the brain from an ischemic insult, presumably through its thrombolytic action. In addition, our study emphasizes the importance of appropriate genetic controls in murine stroke research.

Animals↗
PubMed1998

Intravenous RMP-7 increases delivery of ganciclovir into rat brain tumors and enhances the effects of herpes simplex virus thymidine kinase gene therapy.

Herpes simplex virus thymidine kinase (HSV-tk) gene therapy for brain tumors depends on ganciclovir (GCV) and its transport across the blood-brain tumor barrier (BBTB). We examined whether RMP-7, the bradykinin analog and potent BBTB permeabilizer, could enhance the efficacy of GCV treatment of brain tumors by increasing the BBTB delivery of GCV. In vitro, a significant bystander cytocidal effect of GCV was shown in mixed HSV-tk-transduced (HSV-tk+) and control vector-transduced (HSV-tk-) C6 glioma cultures. A dose-dependent cytotoxic effect of GCV on untransformed C6 cells was also shown. In vivo, rats with 100% HSV-tk+ or 100% HSV-tk- intracerebral C6 gliomas were treated for 7 days with intravenous infusions of GCV alone or with GCV and RMP-7 (2.5 microg/kg/day). The growth of HSV-tk+ and HSV-tk- gliomas decreased with increasing doses of GCV. A high dosage (100 mg of GCV/kg/day) eradicated all HSV-tk- and HSV-tk+ tumors. An intermediate dosage (5 mg of GCV/kg/day) reduced the growth of HSV-tk- gliomas by 42% if given alone, and by 88% in combination with RMP-7. A low dosage (0.5 mg of GCV/kg/day) in combination with RMP-7 enhanced the regression of HSV-tk+ gliomas by 87% compared with GCV alone. Low-dose GCV was ineffective in HSV-tk- tumors. RMP-7 increased [3H] GCV tumoral uptake by 2.6- and 1.7-fold in the tumor center and periphery, respectively. We conclude that RMP-7 could be an important adjunctive treatment for suicide gene therapy of brain tumors, while an RMP-7/GCV combination may also have a significant antitumor effect in untransfected gliomas.

3T3 Cells↗
PubMed1998

Loss of Rb expression in an ACTH-secreting pituitary carcinoma.

Little is known about the molecular mechanisms of tumor progression in the pituitary. However, animal studies suggest that the Rb gene may be involved in the development of pituitary carcinoma. Pathologic examination of a pituitary tumor that included both benign and malignant components provided insight into this mechanism. Both benign and malignant tumors were immunoreactive for ACTH. The benign adenoma showed strong nuclear immunoreactivity for Rb, however, both the adjacent sellar carcinoma and its metastases were Rb-negative. This study suggests that loss of Rb may in some cases be important in the progression of pituitary adenoma to carcinoma.

Adrenocorticotropic Hormone↗
PubMed1998

Prolactinomas express human heparin-binding secretory transforming gene (hst) protein product: marker of tumour invasiveness.

BACKGROUND AND OBJECTIVE: We have shown previously that heparin-binding secretory transforming gene (hst) overexpression in rat pituitary cells mediates lactotroph tumour growth and stimulates PRL transcription, and that transforming sequences of the gene, which encode fibroblast growth factor-4 (FGF-4), are expressed in human prolactinomas. To further determine the role of hst in human PRL-secreting adenoma pathogenesis we studied the presence of hst protein in these tumours and other types of human pituitary adenoma. PATIENTS AND DESIGN: Pituitary adenoma tissue samples were obtained at surgery from 14 patients with PRL-secreting adenomas, 5 patients with GH-secreting tumours, 3 with ACTH-secreting, and 13 patients with nonfunctioning tumours. Two normal pituitary tissue specimens were also studied. Clinical data, including tumour invasiveness assessed by preoperative MRI studies, were available. For hst protein immunolocalization, tumour frozen sections were immunostained with antihuman FGF-4 antibody. Immunoperoxidase staining for the proliferation-related nuclear antigen Ki-67 was performed using MIB-1 monoclonal antibody. RESULTS: Normal anterior pituitary cells did not contain immunoreactive hst protein. Lactotrophs in five of 14 prolactinomas (36%) stained strongly for hst compared with immunoreactive pituicytes in only one of 21 nonfunctioning, GH-, and ACTH-secreting adenomas (P = 0.05). Immunoreactive hst in adenoma cells was detected in 3 of 5 invasive prolactinomas, and in 2 of 9 noninvasive PRL-cell adenomas. Immunostaining for the proliferation-related antigen Ki-67 showed a higher proliferation index in hst-positive adenomas (3.94 + 0.85%) as compared with those immunonegative for hst (1.98 + 0.7%; P = 0.05). CONCLUSIONS: hst protein may be directly involved in prolactinoma development or progression, particularly in invasive tumours, probably due to the growth promoting effects of FGF-4.

Adrenocorticotropic Hormone↗
PubMed1998

Cerebrovascular accumulation and increased blood-brain barrier permeability to circulating Alzheimer's amyloid beta peptide in aged squirrel monkey with cerebral amyloid angiopathy.

Senescent squirrel monkey is a valuable model to study pathogenesis of cerebrovascular amyloid angiopathy (CAA). Cerebrovascular sequestration and blood-brain barrier (BBB) permeability to 121I-amyloid beta(1-40) synthetic peptide (sA beta(1-40)) were studied in adult versus aged squirrel monkey 1 h after a single intravenous injection. In aged monkey, the half-time of elimination of sA beta(1-40), t(1/2)e, was prolonged by 0.6 h, the systemic clearance, ClSS, was reduced from 1.8 to 1.1 ml/min/kg, and the mean residence time of intact peptide in the circulation was increased by 1 h (45%). In adult monkey, cerebrovascular sequestration of intact sA beta(1-40) was significant, and the BBB permeability was 18.6-fold higher than for inulin. In aged monkey, the sequestration of intact sA beta(1-40) by cortical and leptomeningeal microvessels and the BBB permeability were increased by 5.9, 1.8-, and 2.1-fold, respectively, in the presence of an unchanged barrier to inulin. In brain parenchyma of aged animals, 76.1% of circulating sA beta(1-40) remained intact versus 45.7% in adult. We conclude that multiple age-related systemic effects, i.e., reduced body elimination and systemic clearance of sA beta(1-40), and reduced peripheral metabolism, may act in concert with BBB mechanisms, i.e., increased transendothelial transport and microvascular accumulation of blood-borne sA beta(1-40), and reduced brain metabolism to enhance the development of CAA.

Aging↗
PubMed1998

Experience in the surgical management of 82 symptomatic herniated thoracic discs and review of the literature.

OBJECT: The authors aimed to develop management strategies for the treatment of herniated thoracic discs and to define indications for selection of surgical approaches. Symptomatic thoracic discs requiring surgery are rare. Between 1971 and 1995, 71 patients with 82 herniated thoracic discs were surgically treated by the authors. The treated group included 34 men and 37 women whose ages ranged from 19 to 75 years, with a mean age of 48 years. The most common sites of disc herniation requiring surgery were from T-8 to T-11. Evidence of antecedent trauma was present in 37% of the patients. Preoperative symptoms included pain (localized, axial, or radicular) in 54 (76%) of the 71 patients, evidence of myelopathy, that is, motor impairment in 43 (61%), hyperreflexia and spasticity in 41 (58%), sensory impairment in 43 (61%), and bladder dysfunction in 17 (24%). METHODS: Radiological diagnosis for the patients in this series was accomplished by means of myelography, computerized tomography myelography, or magnetic resonance imaging. Classification of the disc location into two groups reveals that 94% were centrolateral and 6% were lateral. Evidence of calcification was present in 65% of patients, and in 7% intradural extension was noted at surgery. Ten patients (14%) were found to have multiple herniations. Four surgical approaches were used for the removal of these 82 disc herniations: transthoracic in 49 (60%), transfacet pedicle-sparing in 23 (28%), lateral extracavitary in eight (10%), and transpedicular in two (2%). Postoperative evaluation revealed improvement or resolution of pain in 47 (87%) of 54, hyperreflexia and spasticity in 39 (95%) of 41, sensory changes in 36 (84%) of 43, bowel/bladder dysfunction in 13 (76%) of 17, and motor impairment in 25 (58%) of 43. Complications occurred in a total of 12 (14.6%) of 82 discs treated surgically. Major complications were seen in three patients and included perioperative death from cardiopulmonary compromise, instability requiring further surgery, and an increase in the severity of a preoperative paraparesis. CONCLUSIONS: Review of this series, with the attendant complications, together with evaluation of several contemporary thoracic disc series, has facilitated the authors' decision-making process when considering the comprehensive management of these patients, including the selection of a surgical approach.

Adult↗
PubMed1998

Excessively high prolactin level in a patient with a nonprolactin-secreting adenoma. Case report.

The authors report the case of a 48-year-old woman who presented with a nonprolactin-secreting adenoma and a preoperative prolactin level of 662 ng/ml. The patient's neoplasm subsequently enlarged despite normalization of her prolactin level with dopamine agonist therapy. Hyperprolactinemia, with levels of prolactin as high as 150 ng/ml, is commonly associated with sellar tumors and is attributed to disruption of the normal delivery of dopamine to the adenohypophysis. The prolactin level found in this patient represents the highest level attributed to the stalk-section effect reported in the literature and underscores the need for repeated radiographic assessment of patients who are undergoing treatment with bromocriptine and have prolactin levels in the 25 to 1000 ng/ml range.

Adenoma↗
PubMed1997

Somatostatin receptor (SSTR) subtype-selective analogues differentially suppress in vitro growth hormone and prolactin in human pituitary adenomas. Novel potential therapy for functional pituitary tumors.

Previously, we have shown somatostatin receptor (SSTR) subtype-specific regulation of growth hormone (GH), thyroid-stimulating hormone, and prolactin (PRL) secretion in human fetal pituitary cultures, where GH and thyroid-stimulating hormone are mediated by both SSTR2 and SSTR5, whereas SSTR2 preferentially mediates PRL secretion. We now tested SSTR subtype-selective analogues in primary human GH- and PRL-secreting pituitary adenoma cultures. Analogue affinities determined by membrane radioligand binding in cells stably expressing human SSTR forms were either SSTR2 or SSTR5-selective. Analogues preferential either for SSTR2, including octreotide, lanreotide, and novel compounds with improved affinity for SSTR2, or new SSTR5-selective compounds suppressed GH in tumor cell cultures (up to 44% of control; P < 0.0005). However, novel analogues from both groups were 30-40% more potent than octreotide and lanreotide in suppressing GH (P < 0.05). Heterologous analogue combinations containing both SSTR2- and SSTR5-selective compounds were more potent in decreasing GH than analogues used alone (P < 0.05), or than combinations of compounds specific for the same receptor subtype (P < 0.005). In contrast, SSTR2-selective analogues did not suppress PRL release from six cultured prolactinomas studied. However, new SSTR5-selective analogues suppressed in vitro PRL secretion (30-40%; P < 0.05) in four of six prolactinomas. These results suggest that both SSTR2 and SSTR5 are involved in GH regulation in somatotroph adenoma cells, whereas SSTR5 exclusively regulates PRL secretion from prolactinoma cells. Thus, somatostatin analogues with improved selective binding affinity for these receptor subtypes may be effective in the treatment of either GH- or PRL-secreting adenomas.

Adenoma↗
PubMed1997

Prognostic variables in surgery for skull base meningiomas.

The authors have retrospectively analyzed selected surgical and pathological observations made among a group of 20 patients harboring recurrent cranial base meningiomas in an attempt to reveal which factors may be important in predicting tumor recurrence. This cohort was compared with a group of 34 patients with cranial base meningiomas that underwent primary resection and in whom tumor recurrence has not been demonstrated over a median follow-up period of 33 months. Features analyzed included brain, cranial nerve, carotid artery, or muscle invasion as well as tumor cellularity, nucleolar prominence, cellular pleomorphism, and percentage of cells staining positive for the Ki-67 antigen. As expected, increased cellularity and tumor necrosis were relatively more prevalent in recurrent tumors. With regard to tumor type, atypical and anaplastic tumors were more common in the group of patients with recurrent tumor compared with the primary group (p < 0.02). As expected, increased cellularity was relatively more prominent in recurrent tumors. Invasion of muscle and bone (72%) was more frequently associated with recurrent tumors, suggesting that these characteristics may be important features of recurrent skull base meningiomas.

Journal Article↗
PubMed1997

Characterization of spherical amyloid protein from a prolactin-producing pituitary adenoma.

Prolactin (PRL)-producing pituitary adenomas are in some cases associated with deposition of abundant spherical amyloid; however, the origin of the amyloid has not been established. In this report, a PRL-producing pituitary adenoma composed almost entirely of spherical amyloid was analyzed biochemically. The tumor was removed surgically from a 56-year-old man. Immunohistochemical analysis revealed that residual tumor cells were strongly positive for PRL, while the spherical amyloid was not. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a band of approximately 4 kDa associated with the amyloid, which was not present in a nonamyloid producing prolactinoma. The 4-kDa band is similar in size to other known amyloidogenic peptides. Immunoblot analysis of the tumor material using polyclonal anti-human PRL antibodies revealed a small amount of normal-sized PRL; however, the abundant 4-kDa band was nonimmunoreactive. Amino acid sequencing showed that this peptide represents the first 34 amino acids of the intact PRL protein with a predicted size of 4313 Da. The presence of a small amount of normal-sized PRL in this tumor, as well as elevated circulating levels of PRL implies that intact PRL is being abnormally processed in the formation of spherical amyloid.

Amino Acid Sequence↗
PubMed1997

Transmaxillary approach to the anterior cavernous sinus: a microanatomic study.

OBJECTIVE: Several approaches to expose the anterior cavernous sinus have been used, such as frontotemporal, orbitofrontal, anterior subtemporal, and various transfacial approaches. In an effort to gain exposure to the anterior cavernous sinus without necessitating a craniotomy or wide transfacial exposure, the authors in the present study have developed a transmaxillary approach to the cavernous sinus. METHODS: The approach was developed using data obtained by performing 24 cadaveric dissections. Using a sublabial incision to expose the maxilla, maxillotomy is performed and the course of the infraorbital nerve is identified as a guide to the maxillary branch of the trigeminal nerve. After an osteotomy of the posterior sinus wall and pterygoid plate, the foramen rotundum is identified, which lies a mean of 10 mm from the posterior wall of the maxilla. A superomedial enlargement of the foramen rotundum is then undertaken to ultimately expose the anterior cavernous sinus. RESULTS: This technique offers access to all cavernous cranial nerves, as well as the entire course of the anterior loop of the internal carotid artery to the origin of the ophthalmic artery. With a mean operative range of 38 mm from the posterior wall of the maxilla to the anterior loop of the internal carotid artery, this approach offers adequate exposure with a short operative distance. CONCLUSION: The approach may be useful in limited exposure of tumors of the anterior cavernous sinus and some intracavernous vascular lesions.

Brain Mapping↗