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J M Piepmeier

Publications and source records attributed to J M Piepmeier.

34 records · Page 2Linked to original sources
PubMed1995

Verapamil treatment attenuates immunoreactive GFAP at cerebral cortical lesion site.

Cerebral cortical lesions were produced using a stereotactic injection system in Sprague-Dawley rats randomly assigned to three groups: (1) needle lesioned and uninjected (Lesioned), (2) needle lesion and simultaneous local injection of 50 or 100 microliters 0.9% saline (L/Saline), and (3) needle lesion and simultaneous local injection of 50 or 100 microliters Verapamil-HCl (VHCL) (2.5 mg/ml (5 mM) Abbott Labs, Chicago, IL), a passive, L-type calcium channel blocker (L/VHCL). The lesioning induced expression of glial fibrillary acidic protein (GFAP), a type of intermediate filament protein expressed in reactive astrocytes, at the lesion site. There was a reduction in GFAP-like immunoreactivity (GFAP-IR) in the L/VHCL group versus the Lesioned and the L/Saline groups. There was a five-fold increase of GFAP-IR at 24 h post lesion in the L/Saline group, but no statistically significant increase seen in the Lesioned or L/VHCL groups at either volume. Pretreatment of the anti-GFAP with VHCL did not impair the antigen labeling. To determine whether differences in pHs, or volume could account for these findings, a second experiment was performed using pH-matched saline or VHCL in 10 microliters volume injected into contralateral hemispheres at the time of lesioning. There was an 80% reduction in GFAP-IR in the L/VHCL group at 72 h compared with the L/Saline group. These data suggest that VHCL may suppress the early increase of GFAP-IR in response to cortical lesion and that reducing transmembrane calcium flux through L-type calcium channels may be the mechanism involved.

Animals↗
PubMed1995

Reconstruction of suboccipital craniectomy defects with hydroxyapatite cement: a preliminary report.

Hydroxyapatite cement, a new biomaterial presently under clinical investigation, has been demonstrated to have potentially wide application in cranial reconstruction. We describe our experience with this biologic bone cement in the reconstruction of suboccipital craniectomy defects in seven patients after vestibular schwannoma removal. With up to 2-year follow-up, cranial bone integrity has been reestablished in five patients. Dissolution of cement has occurred in dependent areas and appears to be technique related. Cranial bone contour appears dependent on the amount of cement used. The frequency of debilitating postoperative headache was reduced in these patients when compared to patients who had no reconstruction of the craniectomy defect. Reconstruction of the bony defect after suboccipital craniectomy with hydroxyapatite cement is not only useful to restore cranial contour, but also appears to reduce some of the functional deficits attributed to this surgical approach.

Biocompatible Materials↗
PubMed1994

Selective antimitotic effects of estramustine correlate with its antimicrotubule properties on glioblastoma and astrocytes.

Estramustine is an estradiol-based agent that accumulates in cells containing estramustine binding protein. Previous studies have shown that this binding site is expressed in human glioblastoma cells and that estramustine accumulates in glioma cells, resulting in a concentration-dependent inhibition of proliferation. We have shown that estramustine treatment results in a rapid inhibition of deoxyribonucleic acid synthesis (within 4 h) in human glioblastoma cells associated with an alteration of cell size and shape, consistent with its known antimicrotubule activity. To extend these findings, we performed an immunohistochemical analysis of microtubules with a monoclonal antibody to beta-tubulin, using a colorimetric assay with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide to measure the antimitotic effects of estramustine on both human glioblastoma and astrocyte cultures. Within 4 hours, estramustine (10 mumol/L) caused a dramatic alteration in the tubulin staining in glioma cells, characterized by a disorganization in microtubules. Cell shape and microtubule staining in astrocytes were relatively preserved. Estramustine had a concentration-dependent cytotoxic effect in tumor cultures, whereas it had no effect on astrocyte viability at any concentration. Differences in the antimitotic effects do not appear to be related to variations in proliferation rates among these different types of cells. These data suggest that although estramustine is a potent inhibitor of proliferation in glioblastoma cells, it has modest antiproliferative effects on astrocytes and its selective activity is closely correlated with its antimicrotubule properties.

Astrocytes↗
PubMed1993

Estramustine and estrone analogs rapidly and reversibly inhibit deoxyribonucleic acid synthesis and alter morphology in cultured human glioblastoma cells.

Estramustine is an estradiol-based agent that has been shown to accumulate in human glioma cells, resulting in a concentration-dependent alteration in cell size and shape within minutes and an inhibition of proliferation over 3 to 6 days. We evaluated human glioblastoma cultures with [3H]thymidine incorporation assays to determine estramustine's early effects on deoxyribonucleic acid synthesis in these tumors. Because estramustine shares a common structural motif with other antimicrotubule drugs, we synthesized four A-ring conjugates of estrone that contained a carbamate moiety but lacked nitrogen mustard. These analogs were examined by [3H]thymidine incorporation and compared with vinblastine. Greater than 70% inhibition of [3H]thymidine incorporation occurred within 1 hour of treatment with estramustine at 10(-5) mol/L, which increased to 80% inhibition at 4 hours. Ethyl carbamate JE208 was nearly as effective as estramustine in inhibiting deoxyribonucleic acid synthesis, and both were more effective than vinblastine. The inhibitory effects of estramustine and estrone analogs were reversible; vinblastine was not reversible. Although estramustine and JE208 induced similar antiproliferative and morphological changes in glioblastoma cells that persisted for at least 4 days, there was a modest recovery of morphology and thymidine incorporation with JE208 after prolonged treatment. The common findings with estramustine and JE208 suggest that these agents may have a similar mechanism of action and form the basis for the investigation of new agents that may rapidly and reversibly inhibit glioblastoma.

Brain Neoplasms↗
PubMed1993

Low-grade astrocytomas may arise from different astrocyte lineages.

The management of low-grade astrocytomas remains a challenge. Although the majority of these tumors have common histological features, they may have very different clinical manifestations and rates of proliferation. Because low-grade astrocytomas are composed of relatively well-differentiated neoplastic cells that closely resemble the astrocytic phenotype, it is possible that some of these lesions express antigens that characterize astrocyte lineages. The authors performed an immunohistochemical analysis of 20 low-grade astrocytomas with A2B5, a monoclonal antibody to a ganglioside found in early postnatal Type 2 (fibrillary) astrocytes, but absent in Type 1 (protoplasmic) astrocytes, and anti-glial fibrillary acidic protein to determine whether the expression of these antigens could be used to determine the histogenesis of these tumors. These findings were compared with the clinical and imaging features of these tumors. The percentages of cells positive for A2B5 and glial fibrillary acidic protein was strongly correlated with the location of the tumor within the cortex or white matter and with the length of preoperative symptoms. Tumors based in the cortex contained significantly fewer A2B5-positive and glial fibrillary acidic protein-positive cells than white matter tumors. In addition, lesions that caused a relatively short period of preoperative symptoms (< 1 year) had significantly more A2B5-positive and glial fibrillary acidic protein-positive cells than lesions responsible for a long preoperative history (mean, 12.9 years). These findings suggest that slow-growing, cortically based low-grade astrocytomas have a phenotype consistent with the Type 1 (protoplasmic) astrocyte lineage, while white matter low-grade astrocytomas express antigens consistent with the Type 2 (fibrillary) astrocyte lineage.

Adolescent↗
PubMed1990

Extensive wounds of the spine: a comprehensive approach to debridement and reconstruction.

Extensive wounds involving the spine (greater than three vertebral segments exposed) may threaten its indispensable roles of biomechanical support and vital neurologic function. Although there have been select reports of specific flap applications in this body region in the reconstructive surgical literature, there has been a paucity of comprehensive descriptions of pertinent anatomy, pathophysiology, and the perioperative care of such patients--including the degree to which the spine is suited to aggressive debridement. Four patients with complex spine wounds involving greater than three vertebral segments were treated by the authors from 1986 through 1988. These patients ranged from 28 to 80 years of age. They were all found to have multiple risk factors, including neoplasm (4), severe nutritional depletion (3), advanced age (2), wound sepsis (2), and multiple other general medical problems (4). All patients underwent wide bony and soft-tissue debridement. A new clinically essential four-pillar concept of spinal support predicted spinal instability in two of the four patients. These patients could thus be protected from neurologic compromise with internal stabilization (1) or external orthotic support (1). Wound closure was achieved with skin graft (1) or traditional or extended musculocutaneous flap coverage (3). With 7 to 20 months of follow-up, wound healing has been complete in all patients despite a 100 percent complication rate and one late postoperative death. Multisegment spine wounds tend to arise in the setting of multiple medical problems or risk factors. Despite these risk factors and a high postoperative complication rate, gratifying results may be achieved in these patients with a comprehensive understanding of regional surgical anatomy and a multidisciplinary approach to their care.

Adult↗
PubMed1988

Primary leptomeningeal sarcomatosis. Case report.

This report describes a case of primary leptomeningeal sarcomatosis in a 50-year-old man who presented with progressive deficits involving multiple cranial nerves and spinal roots. Despite the clinical evidence supporting a diffuse process involving the leptomeninges, radiological, serological, and cerebrospinal fluid examinations failed to reveal the cause of the disorder. Consequently, surgical exploration and biopsy were required to obtain a pathological diagnosis. This case report illustrates the difficulty in diagnosing this disease and supports the use of open biopsy in patients with chronic meningeal disease when the diagnosis cannot be established by less invasive methods.

Humans↗
PubMed1988

Late neurological changes following traumatic spinal cord injury.

Sixty-nine patients with traumatic spinal cord injuries were evaluated for changes in their functional neurological status at discharge from the hospital, and at 1 year, 3 years, and 5+ years following injury. The neurological examinations were used to classify patients' spinal cord injury according to the Frankel scale. This analysis revealed that the majority of improvement in neurological function occurred within the 1st year following injury; however, changes in the patients' status continued for many years. Follow-up examinations at an average of 3 years postinjury revealed that 23.3% of the patients continued to improve, whereas 7.1% had deteriorated compared to their status at 1 year. An examination at an average of 5+ years demonstrated further improvement in 12.5%, with 5.0% showing deterioration compared to the examinations at 3 years. These results demonstrate that, in patients with spinal trauma, significant changes in neurological function continue for many years.

Adolescent↗
PubMed1987

Cardiovascular abnormalities accompanying acute spinal cord injury in humans: incidence, time course and severity.

The frequency of cardiovascular abnormalities was evaluated in 71 consecutive patients with acute injury to the spinal cord. Persistent bradycardia was universal in all 31 patients with severe cervical cord injury and less common in milder cervical injury (6 of 17) or thoracolumbar injury (3 of 23) (p less than 0.00001). Marked sinus slowing (71 versus 12 versus 4%, respectively, p less than 0.00001), hypotension (68 versus 0 versus 0%, p less than 0.00001), supraventricular arrhythmias (19 versus 6 versus 0%, p = 0.05) and primary cardiac arrest (16 versus 0 versus 0%, p less than 0.05) were significantly more frequent in the severe cervical injury group. The frequency of bradyarrhythmias peaked on day 4 after injury and gradually declined thereafter. All observed abnormalities resolved spontaneously within 2 to 6 weeks. The primary mechanism underlying these observations appears to involve the acute autonomic imbalance created by the disruption of sympathetic pathways located in the cervical cord. Acute severe injury to the cervical spinal cord is regularly accompanied by arrhythmias and hemodynamic abnormalities not found with thoracolumbar cord trauma. These abnormalities are limited to the first 14 days after injury, a period in which life-threatening disturbances must be anticipated.

Adolescent↗
PubMed1987

Observations on the current treatment of low-grade astrocytic tumors of the cerebral hemispheres.

The records of 60 patients with low-grade astrocytic tumors of the cerebral hemispheres treated between 1975 and 1985 were examined to evaluate the results of current treatment methods. This analysis revealed that the patient's age and tumor enhancement on computerized tomography (CT) with intravenous administration of contrast material were the only factors that influenced survival time. Compared to prior studies, the patients in this report more frequently had normal preoperative neurological examinations and total resection of their lesions. These differences may have resulted from the use of CT scans over the past decade. Earlier diagnosis and improvement definition of the tumor location and extent are two reasons why the use of CT scans may have affected outcome statistics. A re-examination of treatment methods and the timing of those treatments is needed to define the optimal management of these lesions.

Adult↗
PubMed1985

Cardiovascular instability following acute cervical spinal cord trauma.

Irregularities in vital sign (pulse, blood pressure, cardiac rhythm) recordings are commonly observed following acute spinal cord injury. These abnormalities have been generally attributed to autonomic instability. However, there have been no clinical reports that evaluate these problems in a large group of acutely injured patients. Therefore, this study was performed on 45 patients with acute cervical spinal cord injuries to evaluate the incidence, severity, and risk factors for cardiovascular instability. This investigation revealed that there is a direct correlation between the severity of the cord injury and the incidence and severity of cardiovascular problems. Endotracheal suctioning with or without documented hypoxia are major causes of severe bradycardia and cardiac arrest within the first 2 weeks after trauma. Careful monitoring of severely injured patients and attention to the warning signs of cardiovascular instability can reduce the risk of life-threatening emergencies.

Acute Disease↗
PubMed1983

Laminar distributions of 2-deoxyglucose uptake in the rat spinal cord following electrical stimulation of the sciatic nerve.

The 2-deoxyglucose method was employed to study the functional organization of afferent axons in the dorsal horn of the rat spinal cord. Stimulation of axons in the sciatic nerve with conduction velocities greater than 17 m/s produced activity predominantly in the deep laminae of the dorsal horn. In contrast, stimulation of the entire population produced activity throughout the dorsal horn. The results are discussed in relation to the functional organization of the rat dorsal horn.

Animals↗
PubMed1982

Delayed post-traumatic extracerebral hematomas.

Acute craniocerebral trauma remains a difficult management problems. Optimal conditions for recovery require stabilization of vital signs, removal of a mass lesion when present, and control of intracranial pressure. While computerized tomography (CT) has helped achieve these objectives, there remain patients who may develop a second extracerebral hematoma not evident on their initial preoperative scan. This report concerns our experience with patients who developed such delayed post-traumatic extracerebral hematomas shortly after evacuation of hematomas at other sites. Between 1 January 1979 and 1 October 1980, 47 patients underwent emergency evacuation of a traumatic extracerebral hematoma (38 acute subdural and 18 acute epidural hematomas) at the Yale New Haven Hospital. Within 24 hours, four patients developed, in addition, a total of six delayed extracerebral hematomas (10%) which also required evacuation. In all of these patients a skull fracture was present at the site of the delayed hematomas. This experience suggests: 1) Exploration of extracerebral space beneath a skull fracture should be considered following evacuation of a hematoma at another site. 2) Repeat CT is indicated if anticipated improvement does not occur after evacuation of a hematoma. 3) Decompression of the intracranial contents by removal of a hematoma may promote the development of another delayed hematoma.

Adult↗