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Biomedical subjects

J M Sheehan

Publications and source records attributed to J M Sheehan.

At least 19 recordsLinked to original sources
PubMed2005

DDAVP use in patients undergoing transsphenoidal surgery for pituitary adenomas.

BACKGROUND: Disorders of fluid and sodium regulation, often termed "diabetes insipidus," are a frequent occurrence following surgery for pituitary adenomas. The present study was undertaken to identify the incidence of diabetes insipidus after pituitary surgery and its associated factors. METHODS: A retrospective review of the medical records 300 patients who underwent transsphenoidal surgery for pituitary adenoma was undertaken. Information regarding patient gender, perioperative serum sodium levels and urinary output volumes, tumor size, previous pituitary surgery, tumor subtype, and the use of DDAVP was gathered. A multivariate statistical analysis was performed. FINDINGS: Follow-up data were available on 288 patients. During the inpatient postoperative hospital stay, DDAVP was administered to 19% of all patients and 16% of patients not taking DDAVP preoperatively. Of patients with normal fluid/sodium regulation preoperatively, DDAVP was prescribed for 9% at discharge and 4% at 6 weeks postoperatively. Only 1.4% of patients were taking vasopressing replacement at the time of last follow-up. Significant correlations were found between gender, previous surgery, serum sodium levels, and urine volumes at various time points. Immunohistochemical type of tumor and tumor size were not related to DDAVP requirement. CONCLUSIONS: Transient hypotonic polyuria is frequently encountered after pituitary surgery. However, only a small number of patients will develop a long-term requiring for ongoing medical treatment. Previous surgery, female gender, and elevated serum sodium and urine volumes in perioperative period were associated with DDAVP requirement.

Adenoma↗
PubMed2002

A horseradish peroxidase-light and electron microscopic study of immunoliposomes utilized for intracellular delivery to the rat striatum.

Liposomes can deliver plasmid DNA, viruses, antisense oligonucleotides, and pharmacological agents to the central nervous system. Conjugation of antibodies to liposomes increases delivery specificity. Immunoliposomes created with Thy 1.1 antibody have previously been shown to be effective for neuronal delivery. The intracellular delivery of these immunoliposomes is evaluated by light and electron microscopy. Thy 1.1 conjugated liposomes were loaded with horseradish peroxidase and stereotactically injected into rat striatum. On light microscopy, immunoliposomes were concentrated within 0.2 mm of the injection site 8 h following delivery but, 24 h post-operatively, had diffused more than 0.5 mm from the injection site. With transmission electron microscopy, immunoliposomes were observed entering numerous neurons and some astrocytes in a process distinct from the clathrin-coated pit mechanism. These findings suggest that Thy 1.1 immunoliposomes are effective for intracellular delivery in vivo and their endocytosis occurs independently of a coated pit process. The research has helped to elucidate alternative mechanisms for immunoliposomal delivery. A more fundamental understanding of these attributes is needed to achieve the therapeutic potential of immunoliposomes.

Animals↗
PubMed2001

Effects of solar-simulated radiation dose fractionation on CD1a+ Langerhans cells and CD11b+ macrophages in human skin.

BACKGROUND: There are few human studies investigating the immunosuppressive effects of exposure to solar-simulated radiation (SSR) and its relationship with sunburn/erythema, and few comparative data on the importance of SSR exposure regimens. OBJECTIVES: To evaluate whether SSR-induced erythema is a reliable end-point for assessing damage to antigen-presenting cells (APCs) in human skin. METHODS: We compared the relationship between SSR-induced erythema and alterations in epidermal CD1a+ Langerhans cells (LCs) and CD11b+ macrophages in human volunteers after single exposures to 0, 0.5, 1, 2 or 3 minimal erythema doses (MED). We also investigated whether SSR exposure leads to an accumulation or accommodation of the same end-points by comparing the effects of a relatively low cumulative SSR dose (3 MED) given in varying daily dose fractions (4 x 0.75 MED, 2 x 1.5 MED and 1 x 3 MED). RESULTS: Single SSR exposures induced a dose-dependent increase in erythema. CD1a+ LCs remaining in the irradiated epidermis showed a dose-dependent increase in cell size and altered morphology. Significant depletion of CD1a+ LCs and presence of CD11b+ macrophages only occurred in sites irradiated with 2 MED and 3 MED. Dose fractionation had no effect on the final erythemal response but the 4 x 0.75 MED and 1 x 3 MED protocols were better tolerated than 2 x 1.5 MED for alterations in CD1a+ LC and CD11b+ cell numbers. In contrast, dose fractionation protected against alterations in CD1a+ LC morphology or cell size. CONCLUSIONS: We found that erythema is a poor indicator of alterations in epidermal APCs and that dose fractionation is an important parameter in the immunological effects of ultraviolet radiation.

Adult↗
PubMed2001

Degenerative lumbar stenosis: the neurosurgical perspective.

Degenerative lumbar stenosis is a complex entity caused by predictable patterns of degenerative pathoanatomy. Patients with spinal stenosis are treated by orthopaedic surgeons and neurosurgeons, who often have slightly different ideas regarding treatment strategies. However, data exist to support several recommendations, regarding fusion with or without instrumentation, surgical versus conservative treatment, and limitation of procedures to symptomatic levels. In the current study, the typical patterns of degenerative disease and surgical treatment and a view of the neurosurgical perspective of the treatment of patients with lumbar stenosis are presented.

Decompression, Surgical↗
PubMed2000

Occipital bone graft for atlantoaxial fusion.

BACKGROUND: Instability of the atlantoaxial segment is frequently encountered in neurosurgical practice. Numerous fusion techniques have been employed at this level. Most commonly, arthrodesis is achieved through bone and wire techniques. We have employed the use of suboccipital bone in lieu of iliac crest autograft in order to avoid the significant morbidity associated with iliac crest graft harvest. METHODS: Twenty one patients suffering instability from various etiologies underwent C1-C2 fusion at our institution using occipital bone graft and wire fixation. A small craniectomy was performed near the foramen magnum, and the bone graft was notched and secured in place using wire fixation. Patients were placed in a Philadelphia or Aspen collar for 6-12 weeks postoperatively, and flexion/extension plain film of the cervical spine were used to evaluate fusion. RESULTS: Long term follow up was available on all patients (mean 32 months, range 12-48 months). Fusion was achieved in 81% of patients within 12 weeks. Specifically, 71% (5/7) of rheumatoid patients were successfully fused. All patients with traumatic C1-C2 instability were fused. No complications were associated with the harvest of the occipital bone. CONCLUSION: The results of fusion via this technique are comparable to other reported series of C1-C2 fusion. Additionally, the complications associated with iliac crest graft harvest were avoided by the use of occipital bone graft. Occipital bone appears to be a suitable bone graft substance for fusion of the C1-C2 level.

Arthritis, Rheumatoid↗
PubMed2000

Protection by ultraviolet A and B sunscreens against in situ dipyrimidine photolesions in human epidermis is comparable to protection against sunburn.

Sunscreens prevent sunburn and may also prevent skin cancer by protecting from ultraviolet-induced DNA damage. We assessed the ability of two sunscreens, with different spectral profiles, to inhibit DNA photodamage in human epidermis in situ. One formulation contained the established ultraviolet B filter octyl methoxycinnamate, whereas the other contained terephthalylidene dicamphor sulfonic acid, a new ultraviolet A filter. Both formulations had sun protection factors of 4 when assessed with solar simulating radiation in volunteers of skin type I/II. We tested the hypothesis that sun protection factors would indicate the level of protection against DNA photodamage. Thus, we exposed sunscreen-treated sites to four times the minimal erythema dose of solar simulating radiation, whereas vehicle and control sites were exposed to one minimal erythema dose. We used monoclonal antibodies against thymine dimers and 6-4 photoproducts and image analysis to quantify DNA damage in skin sections. A dose of four times the minimal erythema dose, with either sunscreen, resulted in comparable levels of thymine dimers and 6-4 photoproducts to one minimal erythema dose +/- vehicle, providing evidence that the DNA protection factor is comparable to the sun protection factor. The lack of difference between the sunscreens indicates similar action spectra for erythema and DNA photodamage and that erythema is a clinical surrogate for DNA photodamage that may lead to skin cancer.

Adolescent↗
PubMed2000

Results of transsphenoidal surgery for Cushing's disease in patients with no histologically confirmed tumor.

OBJECTIVE: Pathological confirmation of surgical resection of an adenoma for Cushing's disease is not always achieved. We reviewed our experience to determine the prognostic significance of this lack of confirmation regarding outcome, and we evaluate explanations for this situation. METHODS: The records of all patients undergoing transsphenoidal surgery for Cushing's disease from 1992 to 1998 were reviewed, and those with no histological confirmation of tumor were identified. Information regarding preoperative and postoperative hormonal levels and clinical symptoms, preoperative magnetic resonance imaging data, intraoperative findings, and the number of reoperations were recorded. RESULTS: There were 29 patients with no confirmation of tumor. Nineteen (66%) of these patients were cured with surgery and only one had a recurrence of disease, with an average follow-up of 38 months. An abnormality thought to represent an adenoma at the time of surgery was removed in 26 patients (90%). Preoperative magnetic resonance imaging suggested a discrete lesion in 21 patients (72%). Neither intraoperative impression nor magnetic resonance imaging appearance was correlated with outcome. CONCLUSION: Patients with no histological confirmation of tumor after transsphenoidal surgery for Cushing's disease are likely to have a good outcome. The results do not differ significantly from reported cure rates in patients with confirmed adenomas. Possible explanations for this situation are discussed.

Adenoma↗
PubMed2000

Resolution of tonsillar herniation and syringomyelia after supratentorial tumor resection: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: The pathophysiological features of syringomyelia are not yet entirely understood. We present a case of a supratentorial mass causing tonsillar herniation and syringomyelia. CLINICAL PRESENTATION: A 51-year-old woman underwent magnetic resonance imaging for evaluation of progressive headaches. A large parieto-occipital mass was revealed. Herniation of the cerebellar tonsils and a cervical syrinx were also noted. INTERVENTION: A craniotomy was performed without incident. After tumor resection, the tonsils ascended and the syrinx resolved in a 1-year period. CONCLUSION: This case highlights the importance of tonsillar herniation in the pathogenesis of syringomyelia. "Acquired" Chiari malformations and syringomyelia attributable to supratentorial masses may be treated by mass resection alone, without the need for foramen magnum decompression.

Female↗
PubMed2000

Radiosurgery for Cushing's disease after failed transsphenoidal surgery.

OBJECT: Although transsphenoidal surgery has become the standard of care for Cushing's disease, it is often unsuccessful in normalizing cortisol production. In this study the authors investigate the safety and efficacy of gamma knife radiosurgery (GKRS) for Cushing's disease after failed transsphenoidal surgery. METHODS: The records of all patients who underwent GKRS at the authors' institution after unsuccessful transsphenoidal surgery for Cushing's disease were retrospectively reviewed. Successful treatment was considered a normal or below-normal 24-hour urinary free cortisol (UFC) level. Records were also evaluated for relapse, new-onset endocrine deficiencies, interval change in tumor size, and visual complications. Forty-three patients underwent 44 gamma knife procedures with follow up ranging from 18 to 113 months (mean 39.1, median 44 months). Normal 24-hour UFC levels were achieved in 27 patients (63%) at an average time from treatment of 12.1 months (range 3-48 months). Three patients had a recurrence of Cushing's disease at 19, 37, and 38 months, respectively, after radiosurgery. New endocrine deficiencies were noted in seven patients (16%). Follow-up magnetic resonance images obtained in 33 patients revealed a decrease in tumor size in 24, no change in nine, and an increase in size in none of the patients. One patient developed a quadrantanopsia 14 months after radiosurgery despite having received a dose of only 0.7 Gy to the optic tract. CONCLUSIONS: Gamma knife radiosurgery appears to be safe and effective for the treatment of Cushing's disease refractory to pituitary surgery. Delayed recurrences and new hormone deficiencies may occur, indicating the necessity for regular long-term follow up.

Adenoma↗
PubMed2000

Chemotherapy for esthesioneuroblastomas.

Esthesioneuroblastoma can be regarded as a chemosensitive tumor based on multiple reports of response to treatment. Neoadjuvant therapy is seldom curative, however, and may be of no benefit in some patients. Individuals who respond to preoperative therapy have a greater chance of long-term disease-free survival. Platinum-based therapy has been the mainstay of treatment. Toxicity has been mild, and treatment failures have been treated with postoperative chemotherapy with or without bone marrow transplantation. Given the small number of cases of esthesioneuroblastoma diagnosed annually, it is unlikely that any consensus on this issue is forthcoming. Either post- or presurgical treatment of advanced stage or recurrent disease has become the standard of care, however.

Adult↗
PubMed1999

In situ repair of cyclobutane pyrimidine dimers and 6-4 photoproducts in human skin exposed to solar simulating radiation.

DNA repair is crucial to the integrity of the human genome. The ultraviolet radiation portion of solar radiation is responsible for the rising incidence of skin cancer, one of the most common types of cancer in humans. We applied a recently developed 32P-postlabeling technique to measure the in situ DNA repair efficiency of solar-simulated radiation induced cyclobutane pyrimidine dimers and 6-4 photoproducts in the skin of nine healthy volunteers with skin type II. Our results show about 6-fold interindividual variations in the level of DNA damage after exposure to an equal biologic dose - 2 minimal erythema doses. The kinetics of DNA repair indicated a base sequence dependence of the repair process. The DNA repair efficiency showed a 20-fold difference in volunteers. An age-related decrease of DNA repair capacity was observed; however, the data are limited due to a small number of subjects and a narrow age range. The variable response in DNA damage levels and individual differences in DNA repair efficiency suggest a susceptible subgroup of people probably with a higher skin cancer risk.

Adult↗
PubMed1999

Factors associated with hydrocephalus after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Associations among various factors and the occurrence of hydrocephalus after aneurysmal subarachnoid hemorrhage (SAH) were evaluated retrospectively in 897 patients enrolled in the North American study of tirilazad mesylate. METHODS: Patients were assessed for hydrocephalus in a blinded fashion. Assessment of hydrocephalus was made on the basis of 3-month follow-up computed tomographic studies or, for those without a 3-month follow-up scan, on the basis of the latest computed tomographic studies obtained at least 10 days after SAH. Criteria indicating the occurrence of hydrocephalus were the presence of significantly enlarged temporal horns or prior placement of a ventricular shunt. Univariate analysis was performed to assess relationships among various factors and hydrocephalus. Factors statistically associated with the occurrence of hydrocephalus were analyzed further using logistic regression analysis. RESULTS: Overall, 25.9% of the 897 patients developed hydrocephalus. Statistically significant associations among the following factors and hydrocephalus were observed (P value; risk coefficient): 1) severity of 3-month post-SAH Glasgow Outcome Scale (0.0001; 2.00); 2) increased ventricular size at admission (0.0001; 2.78); 3) neurological grade severity at admission (0.0274; 1.26); 4) preexisting hypertension (0.0284; 1.66); 5) alcoholism (0.0066; 2.30); 6) female sex (0.0056; 0.49); 7) increased aneurysm size (0.0239; 0.56); 8) pneumonia (0.0299; 1.78); 9) meningitis (0.0290; 5.86); and 10) intraventricular hemorrhage at admission (0.0414; 1.64). CONCLUSION: Hydrocephalus seems to have a multifactorial etiology. Knowledge of risk factors related to the occurrence of hydrocephalus may help guide neurosurgeons in the long-term care of patients who have experienced aneurysmal SAH.

Adult↗
PubMed1998

Tanning in human skin types II and III offers modest photoprotection against erythema.

We have investigated the photoprotective properties of tanning using erythema as an endpoint. Previously unexposed buttock skin sites of 16 young, healthy adults (8 skin type II, and 8 skin type III) were exposed daily (Mon-Fri) for 2 weeks to 0.5 and 0.75 minimal erythema doses (MED) of solar-simulated radiation (SSR). Erythema and melanin levels were assessed daily both visually and quantitatively using a reflectance device. One week after the last tanning treatment, MED reassessments were made on pretreated sites and on adjacent nontreated sites, including sites from which stratum corneum was removed by tape stripping. Compared to skin type II, similar daily SSR treatments produced less erythema and more evident tanning in skin types III. Independent of skin type, all volunteers showed an increased MED value when assessed on the 0.75 MED- and 0.5 MED-treated sites compared to the MED value assessed on adjacent untreated sites. We express any increase in MED as an induced protection factor (IPF), i.e. (MED post-tan/MED pre-tan). Our data show mean IPF of 1.4 and of 2.1 in the 0.5 and 0.75 MED-treated sites respectively, in skin types II. Similar values were obtained in skin types III with IPF of 1.5 and 2.3 for the 0.5 and 0.75 MED-treated sites, respectively. In all cases, removal of the stratum corneum lowered the IPF by about 20%. Our results show that SSR-induced melanogenesis, whether in skin type II or III, offers only moderate protection against erythema and suggest that SSR-induced stratum corneum thickening affords less photoprotection than tanning.

Adult↗
PubMed1997

Partial pediculectomy in the treatment of lumbar spinal stenosis: technical note.

OBJECTIVE: We note an additional pathological condition associated with lumbar spinal stenosis that may be responsible for significant postoperative pain. Recognizing that nerve roots are stretched around hypertrophic pedicles in some cases of spinal stenosis, we have altered our surgical management of these cases to address what may be a previously unrecognized but significant anatomic pathological finding. SURGICAL TECHNIQUE: After ipsilateral posterior bony decompression of the spinal canal, the nerve root is examined as it courses around the pedicle. If the root appears stretched, the medial part of the pedicle is removed using first a diamond bit and then a curet. The nerve root is retracted and protected during this procedure. RESULTS: Inspection of the root after partial pediculectomy frequently reveals lateral movement of the root into space previously occupied by the pedicle. Anatomically, the nerve is better decompressed and free of obstruction. This technique adds little time to the overall duration of the operation. CONCLUSION: Anatomic evidence obtained through intraoperative examination and preoperative imaging techniques indicates that partial pediculectomy may play a role in the treatment of some cases of lumbar stenosis.

Decompression, Surgical↗
PubMed1997

Utilization of type I collagen gel, demineralized bone matrix, and bone morphogenetic protein-2 to enhance autologous bone lumbar spinal fusion.

Autologous bone grafts are currently considered "gold standard" material for achieving long-term spinal arthrodesis. The present study was performed to determine whether demineralized bone matrix (DBM), type I collagen gels, or bone morphogenetic protein-2 (BMP-2) can improve autologous bone spinal fusions. Using a unilateral decompression-contralateral fusion technique in dogs, each of these materials was added to an autologous bone graft. Volumetric analysis, histological analysis, and biomechanical testing were performed to assess the effectiveness of each material. The DBM had an inhibitory effect on solid bone fusion of the spine, whereas the type I collagen gels improved the bony interface between the graft and the host spine. The BMP-2 strongly enhanced the amount of bone deposition at the fusion site and increased the number of intervertebral levels that were solidly fused. This study strongly supports the use of BMP-2 as an additive to autologous bone grafts in spine stabilization.

Animals↗
PubMed1996

Molecular methods of enhancing lumbar spine fusion.

OBJECTIVE: An optimal method for spinal fusion would induce rapid growth of bone via an osteoconductive and osteoinductive implant. This study examines the spinal fusion enhancement potential of some osteoconductive and osteoinductive biomaterials. METHODS: Four similar canines received unilateral posterolateral fusions on the left side at T13-L1 and L4-L5 and on the right side at L2-L3 and L6-L7. The experiments were grouped as follows: Group A, autogenous bone harvested from the iliac crest; Group B, autogenous bone and collagen; Group C, no implant; and Group D, autogenous bone, collagen, and recombinant human bone morphogenetic protein-2. Radiographic assessment, three-dimensional computed tomographic volumetric analysis, and biomechanical testing were performed at each level. RESULTS: For Groups A and B, the fusions demonstrated moderate bone formation at 6 and 12 weeks postoperatively. Group D fusions exhibited earlier and more dramatic increases in volume and radiodensity and eventually were comparable in size to the vertebral bodies. Average fusion volumes computed from three-dimensional computed tomographic analysis were: Group A = 1.243 cc, Group B = 0.900 cc, Group C = 0.000 cc, and Group D = 6.668 cc (P = 0.003 compared to Group A). Group D exhibited flexion and extension biomechanical properties much greater than controls. The addition of recombinant human bone morphogenetic protein-2 consistently yielded the strongest fused segments and, on average, enhanced extension stiffness by 626% and flexion stiffness by 1120% over controls. CONCLUSION: The most advantageous spinal fusion implant matrix consisted of recombinant human bone morphogenetic protein-2, autogenous bone, and collagen. Future investigators, however, need to examine the appropriate quantities of the individual components and clarify the efficacy of the matrix for the various types of spinal fusion approaches.

Animals↗