Biomedical subjects

Jonas M Sheehan

Publications and source records attributed to Jonas M Sheehan.

11 recordsLinked to original sources

PubMed2006

Interleukin-13 receptor-targeted nanovesicles are a potential therapy for glioblastoma multiforme.

The difficulties associated with treatment of malignant brain tumors are well documented. For example, local infiltration of high-grade astrocytomas prevents the complete resection of all malignant cells. It is, therefore, critical to develop delivery systems for chemotherapeutic agents that ablate individual cancer cells without causing diffuse damage to surrounding brain tissue. Here, we describe sterically stable human interleukin-13 (IL-13)-conjugated liposomes, which efficiently bind to the brain cancer cells that overexpress the IL-13 receptor alpha2 protein. The conjugated liposomes bind to glioblastoma multiforme tissue specimens but not to normal cortex. Conjugating the liposomes with human IL-13 allows for specific binding to glioma cells and uptake of the liposomes via endocytosis. Delivering doxorubicin to glioma cells by IL-13-conjugated liposomes results in enhanced cytotoxicity and increased accumulation and retention of drug in the glioma cells compared with delivery of free drug. The therapeutic potential and targeting efficacy of the IL-13-conjugated liposomes carrying doxorubicin was tested in vivo using a s.c. glioma tumor mouse model. Animals receiving i.p. injections of IL-13-conjugated liposomes carrying doxorubicin for 7 weeks had a mean tumor volume of 37 mm3 compared with a mean volume of 192 mm3 in animals injected with nontargeted liposomes. These results strongly suggest that IL-13-conjugated liposomes carrying cytotoxic agents are a feasible approach for creating a nanovesicle drug delivery system for brain tumor therapy.

Animals↗

PubMed2006

Endoscopic extruded screw removal after anterior cervical disc fusion: technical case report.

OBJECTIVE AND IMPORTANCE: Symptomatic complications related to screw migration and extrusion after anterior cervical disc fusion are uncommon. CLINICAL PRESENTATION: We report a case of significant dysphagia owing to late screw migration. INTERVENTION: An endoscopic transpharyngeal removal was performed without pharyngeal closure and with relief of symptoms. CONCLUSION: A transpharyngeal endoscopic approach to remove loose anterior cervical hardware is feasible and warrants further evaluation.

Bone Screws↗

PubMed2005

Pioneers in the development of neurological surgery in Auckland, New Zealand: Robertson, Wrightson, and Mackenzie.

OBJECTIVE: To demonstrate the development of neurosurgery in Auckland, New Zealand, which has diverse roots and was influenced by geographical, socioeconomic, and international forces. METHODS: Historical records were examined, and interviews were conducted to determine the factors that shaped the development of neurological surgery in Auckland, New Zealand. RESULTS: Sir Carrick Robertson, a Scotsman, was one of the more enterprising general surgeons in Auckland. As early as the 1920s, he performed and published the results of several neurosurgical procedures. Later, Donald Mackenzie, another Auckland general surgeon, went abroad to gain neurosurgical experience from his North American and British colleagues. He returned and founded the Auckland Neurosurgical Department in 1945. David Robertson and Phillip Wrightson later joined the department, and they were instrumental in conducting early research on shunt systems, head injury, and pituitary tumors. The neurosurgical department Mackenzie founded went on to become the largest in New Zealand and presently serves metropolitan Auckland as well as both rural areas of New Zealand's North Island and many smaller Pacific island nations. CONCLUSION: Neurological surgery in Auckland was influenced largely by Great Britain, Australia, and North America, as well as by geographical and socioeconomic factors unique to the South Pacific. The achievements of these earlier pioneers in neurosurgery highlight their tremendous abilities and sheer determination to succeed.

History, 18th Century↗

PubMed2005

Stereotactic radiosurgery for pituitary adenomas: an intermediate review of its safety, efficacy, and role in the neurosurgical treatment armamentarium.

OBJECT: Pituitary adenomas are very common neoplasms, constituting between 10 and 20% of all primary brain tumors. Historically, the treatment armamentarium for pituitary adenomas has included medical management, microsurgery, and fractionated radiotherapy. More recently, radiosurgery has emerged as a viable treatment option. The goal of this research was to define more fully the efficacy, safety, and role of radiosurgery in the treatment of pituitary adenomas. METHODS: Medical literature databases were searched for articles pertaining to pituitary adenomas and stereotactic radiosurgery. Each study was examined to determine the number of patients, radiosurgical parameters (for example, maximal dose and tumor margin dose), duration of follow-up review, tumor growth control rate, complications, and rate of hormone normalization in the case of functioning adenomas. A total of 35 peer-reviewed studies involving 1621 patients were examined. Radiosurgery resulted in the control of tumor size in approximately 90% of treated patients. The reported rates of hormone normalization for functioning adenomas varied substantially. This was due in part to widespread differences in endocrinological criteria used for the postradiosurgical assessment. The risks of hypopituitarism, radiation-induced neoplasia, and cerebral vasculopathy associated with radiosurgery appeared lower than those for fractionated radiation therapy. Nevertheless, further observation will be required to understand the true probabilities. The incidence of other serious complications following radiosurgery was quite low. CONCLUSIONS: Although microsurgery remains the primary treatment modality in most cases, stereotactic radiosurgery offers both safe and effective treatment for recurrent or residual pituitary adenomas. In rare instances, radiosurgery may be the best initial treatment for patients with pituitary adenomas. Further refinements in the radiosurgical technique will likely lead to improved outcomes.

Adenoma↗

PubMed2003

Acute and long-term management of sports-related closed head injuries.

Aggressive participation in athletics is rewarded in many ways in our society. As long as there is such strong impetus for participation in athletics, the risks of head injuries for participants will remain. Important strides made in understanding of the pathophysiology of head injuries may lead to improved treatment strategies in the future. In light of the current lack of effective therapies, however, the best options remain injury prevention, early and appropriate recognition, and limitation of subsequent, further injury. Frequently the medical staff is encouraged to allow the athlete to return to play based on the desires of the coach, team, fans, parents, and even the athlete himself. A thorough understanding of the potentially serious risks of repetitive injury, however, mandates that only a proper conservative period of observation and evaluation will best serve the competitor.

Acute Disease↗

PubMed2003

Reflections on shunt infection.

The placement and revision of ventriculoperitoneal (VP) shunts remains a mainstay in the surgical treatment of hydrocephalus. While the North American infection rate averages nearly 8-10%, published infection rates for VP shunt infection below 1% have been reported. We retrospectively reviewed shunt operations by a single surgeon over 62 months to analyze the infection rate. In 62 months, we performed 526 shunt placements or revisions in patients up to 18 years of age. There were 7 shunt infections (1.33%). In 5 cases, the organism was Staphylococcus epidermidis, and a single shunt each was infected with Haemophilus influenzae and Staphylococcus aureus. Each infection was treated with external ventriculostomy drainage and intravenous antibiotics. The new shunt was placed at a new incision site after at least 5 days of sterile spinal fluid cultures. The mean follow-up among these patients after shunt insertion was 25 months. VP shunting remains the most common operation for hydrocephalus. Infections are linked with seizures, higher future risks of shunt infection and malfunction, and reduced IQ and school performance. Our infection rate during 62 months was limited to 1.33%. Uniform surgical technique, limited hardware and skin edge manipulation and double gloving may be important factors in limiting shunt infections.

Adolescent↗

PubMed2003

The safety and utility of recombinant human bone morphogenetic protein-2 for cranial procedures in a nonhuman primate model.

OBJECT: The goal of this study was to evaluate the safety and efficacy of recombinant human bone morphogenetic protein 2 (rhBMP-2) in cranial applications. METHODS: Critical-sized calvarial defects were created bilaterally in four rhesus monkeys, and bilateral rectangular bone flaps were created in six others. Control and rhBMP-2-treated sides were randomly chosen for each animal, and an absorbable collagen sponge was used to deliver the growth factor. Over a 6-month period postoperatively, the animals were serially evaluated for bone healing and adverse BMP-related consequences by using the following methods: computerized tomography (CT) scanning, magnetic resonance (MR) imaging, electroencephalography, histological investigations, and cerebrospinal fluid (CSF) analysis. The critical-sized defects for the rhBMP-2-treated and control sides attained 71 +/- 12% and 28 +/- 11% closure, respectively (four animals; p = 0.04). The CT scans demonstrated that the bone flaps treated with rhBMP-2 had complete osteointegration in five of six animals, whereas scans of the untreated bone flaps demonstrated uniformly poor osteointegration with the intact skull. Histological analysis confirmed well-formed bridges of bone on the rhBMP-2-treated sides. No epileptogenic activity was detected in any of the animals, and MR imaging revealed no evidence of adverse effects on the brain parenchyma. Meningitic irritation was not found on postoperative CSF sample analysis. CONCLUSIONS: Treatment of bone flaps and critical-sized cranial defects with rhBMP-2 leads to improved bone formation and osteointegration in nonhuman primates. Initial evaluation of rhBMP-2 appears to indicate a good safety profile for use in cranial procedures in primates.

Animals↗

PubMed2002

Stress fracture of the pedicle after extensive decompression and contralateral posterior fusion for lumbar stenosis. Report of three cases.

Lumbar spinal stenosis can be effectively treated by performing an extensive ipsilateral spinal decompression, including a partial pediculotomy, and contralateral posterior bone fusion. Infrequently, complications can arise following radical decompression to alleviate symptoms of stenosis, and one such complication is a pedicle fracture. Three reports of pedicle fractures following extensive spinal decompression and contralateral posterior fusion are detailed. This complication is emphasized, and interventions are discussed. Three patients presented with symptoms attributable to lumbar stenosis; they were initially treated with an ipsilateral decompression, achieved in part, through a partial pediculotomy followed by contralateral autologous bone fusion. Initially, all three patients improved postoperatively; however, they later developed neurological symptoms ipsilateral to the side of spinal decompression. Computerized tomography scanning demonstrated pedicle fractures on the decompressed side. This complication has not yet been reported in association with decompression and fusion for lumbar stenosis. Two of the patients developed leg pain necessitating reoperation whereas the third experienced only mild transient symptoms. The fractured pedicle was removed in one patient; laminar and spinous process fusion was performed again. Another patient underwent a total laminectomy, removal of the fractured pedicle, and bilateral transverse process fusion. Reoperation yielded satisfactory outcomes. The third patient's symptoms resolved without intervention. Pedicle fractures are a potential complication of extensive lumbar decompression and contralateral posterior fusion. Loading forces from the facets or transverse processes are possibly the cause of such fractures. Removal of the fractured pedicle, additional decompression, and enhanced bone fusion are recommended when the symptoms warrant surgical intervention.

Aged↗

PubMed2002

Esthesioneuroblastoma: clinical presentation, radiological, and pathological features, treatment, review of the literature, and the University of Virginia experience.

Esthesioneuroblastoma is a rare and malignant upper nasal cavity neoplasm involving the anterior skull base. Treatment includes surgery, radiotherapy, chemotherapy, or a combination. The ideal treatment modality has yet to be determined. Esthesioneuroblastoma often lies in proximity to the optic nerves, optic chiasm, and the orbit. Resection risks damaging these critical structures, and radiotherapeutic techniques, similar to those applied for paranasal sinus tumors, may damage these vital structures and result in late sequelae such as blindness and cortical necrosis. Management strategies for this neoplasm lack uniformity, and there is no universally accepted staging system. In this paper the authors discuss the clinical presentation, radiological and pathological features, and treatment of this rare, malignant skull base neoplasm, as well as review the literature. They also present their results and treatment regimen, which includes preoperative radio- and chemotherapy or 1) craniofacial resection if the lesion has a significant intracerebral component, or 2) frontal sinus resection if little intracranial extension exists.

Adolescent↗

PubMed2002

Thoracic diastematomyelia with concurrent intradural epidermoid spinal cord tumor and cervical syrinx in an adult. Case report.

Diastematomyelia is a rare entity in which some portion of the spinal cord is split into two by a midline septum. Most cases occur in childhood, but some develop in adulthood. A variety of concurrent spinal anomalies may be found in patients with diastematomyelia. The authors describe a 38-year-old right-handed woman who presented with a 7-month history of lower-extremity pain and weakness on the right side. She denied recent trauma or illness. Sensorimotor deficits, hyperreflexia, and a positive Babinski reflex in the right lower extremity were demonstrated on examination. Neuroimaging revealed diastematomyelia extending from T-1 to T-3, an expanded right hemicord from T-2 to T-4, and a C6-7 syrinx. The patient underwent T1-3 total laminectomies, resection of the septum, untethering of the cord, and excision of the hemicord lesion. The hemicord mass was determined to be an intramedullary epidermoid cyst; on microscopic evaluation the diastematomyelia cleft was shown to contain fibroadipose connective tissue with nerve twigs and ganglion cells. Postoperatively, the right lower-extremity pain, weakness, and sensory deficits improved. Diastematomyelia can present after a long, relatively asymptomatic period and should be kept in the differential diagnosis for radiculopathy, myelopathy, tethered cord syndrome, or cauda equina syndrome. Numerous spinal lesions can be found in conjunction with diastematomyelia. To the authors' knowledge, this is the first case in which a thoracic epidermoid cyst and cervical syrinx occurred concurrently with an upper thoracic diastematomyelia. Thorough neuraxis radiographic evaluation and surgical treatment are usually indicated.

Adult↗

PubMedDate not supplied

Stereotactic radiosurgery for pituitary adenomas: a review of the literature.

OBJECTIVE: Pituitary adenomas are very common neoplasms and represent between 10 and 20% of all primary brain tumors. Historically, the treatment armamentarium for pituitary adenomas included medical management, microsurgery, and fractionated radiotherapy. More recently, radiosurgery has emerged as a viable treatment option. The goal of this research is to define accurately the efficacy, safety, and role of radiosurgery for treatment of pituitary adenomas. METHODS: Medical literature databases from 1965 to 2003 were searched for articles pertaining to pituitary adenomas and stereotactic radiosurgery. Each study was evaluated for the number of patients, radiosurgical parameters (e.g. tumor margin dose), length of follow-up, tumor growth control rate, complications, and rate of hormonal normalization in the case of functioning adenomas. RESULTS: A total of 34 published studies including 1567 patients were reviewed. Radiosurgery offers a tumor growth control rate of approximately 90%. The reported rates of hormonal normalization for functioning adenomas vary substantially. This range is in part due to widespread differences in endocrinological criteria utilized for post-radiosurgical assessment. Thus far, the risks of radiation induced neoplasia and cerebral vasculopathy associated with radiosurgery appear to be lower than for fractionated radiation therapy. The incidence of other serious complications following radiosurgery is quite low. CONCLUSIONS: Although surgical resection typically is the primary treatment modality, stereotactic radiosurgery offers safe and effective treatment for recurrent or residual pituitary adenomas. In rare instances, radiosurgery may be the best initial treatment for patients with pituitary adenomas. Refinements in the radiosurgical technique will likely lead to improved outcomes.

Adenoma↗