bluuebunny/crossref_metadata_2025 huggingface dataset:
Tuberculosis of the Axis in a Patient with Systemic Sarcoidosis: Technique of Posterior Open Biopsy of the Dens: Case Report
Authors: Belanger Eric , Levi Allan D. O.
Published: September 2004

OBJECTIVE AND IMPORTANCE

This case report illustrates the importance of obtaining tissue from a destructive lesion of the dens in a patient with systemic sarcoidosis. Although sarcoidosis can involve the axial skeleton, tissue obtained at the time of C1–C2 fusion demonstrated unsuspected pathological features, which dramatically altered the subsequent medical treatment. The technique of open posterior biopsy of the dens is illustrated, and the advantages of the approach are discussed.

CLINICAL PRESENTATION

A 40-year-old woman with systemic sarcoidosis developed neck pain and atlantoaxial instability. Imaging revealed multiple thoracic and cervical vertebral abnormalities, including a destructive enhancing lesion involving the base of the dens.

INTERVENTION

At the time of posterior C1–C2 fusion, we elected to perform an open biopsy of the base of the dens. A 16-gauge biopsy needle was introduced along the medial portion of the left C2 pars, aiming medially toward the base of the odontoid process. This procedure was performed under direct observation, with fluoroscopic guidance. The biopsy specimen contained caseating granulomas, and cultures were positive for Mycobacterium tuberculosis.

CONCLUSION

The unusual presentation, the technique, and the importance of obtaining tissue to confirm the diagnosis of tuberculous involvement of the dens are emphasized. The relationship between sarcoidosis and tuberculosis reported in the literature is reviewed. In the current case, cell wall-positive tuberculous bacteria were cultured, confirming the presence of two separate diseases in the same patient.
Molecular Biology of Degenerative Disc Disease
Authors: Guiot Bernard H. , Fessler Richard G.
Published: September 2004

THE INTERVERTEBRAL DISC is a complex anatomic and biochemical structure. It is composed primarily of fibrocytes and chondrocytes that are anatomically segregated in an elaborate avascular macromolecular matrix of collagen and proteoglycans. Degenerative processes associated with aging and trauma result in morphological and molecular changes to the disc. Morphological changes are observed as dehydration, fissuring, and tearing of the nucleus, annulus, and endplates. On the molecular level, degenerative changes include decreased diffusion, decreased cell viability, decreased proteoglycan synthesis, and alteration in collagen distribution. The role of inflammatory mediators in these processes, and the potential use of growth factors to delay or reverse the degenerative cascade, is poorly understood. However, these areas are under active investigation, the results of which may soon contribute significantly to our understanding of degenerative disc disease.
Transcranial Brainstem Stab Injuries: A Retrospective Analysis of 17 Patients
Authors: Nathoo Narendra , Boodhoo Hemraz , Nadvi Syed Sameer , Naidoo Steven R. , Gouws Eleanor
Published: September 2004

OBJECTIVE

Transcranial stab injuries remain a frequent cause of emergent neurosurgical admissions to neurosurgical units in South Africa. Brainstem stabs are an uncommon, yet often fatal, form of brain injury.

METHODS

A retrospective audit of 597 patients with transcranial stab injuries admitted to our unit over a 12-year period (January 1987 to December 1998) identified 17 patients (2.85%) with brainstem stab injuries. The computed tomographic scans of all patients were analyzed, and a detailed autopsy examination of the skull and its contents was performed in all patients who died. Stepwise linear regression analysis was used to formulate a predictive model of outcome for the entire series of 597 patients.

RESULTS

The majority of the patients were males (16 patients), and the study group had a mean age of 28.65 ± 9.59 years and a mean Glasgow Coma Scale score of 8.59 ± 2.76. Knives (82%) were the most common instruments of penetration. Cerebral angiography identified 3 patients with vascular abnormalities, and autopsy revealed an additional 4 patients with vascular injury. Emergency ventriculostomy was performed in 10 patients for obstructive hydrocephalus. Four of the 17 patients survived (76.5% mortality). Factors significantly predictive of outcome in patients with transcranial stab injuries were the Glasgow Coma Scale score (F = 43.7), the occurrence of intraventricular hemorrhage (F = 22.8), the type of associated lesion (intracranial bleed, vascular abnormality, or brain abscess) (F = 5.9), and the number of operations (F = 3.2).

CONCLUSION

The Glasgow Coma Scale score is the most significant predictor of outcome in low-velocity transcranial stab injuries. Brainstem stab injuries have a great propensity for vascular damage. Survivors are incapacitated by severe, fixed neurological deficits.
The Efficacy and Cost of Prophylactic and Periprocedural Antibiotics in Patients with External Ventricular Drains
Authors: Alleyne Cargill H. , Hassan Mahmood , Zabramski Joseph M.
Published: September 2004

OBJECTIVE

Prophylactic antibiotics are routinely administered to patients with external ventricular drains (EVDs); however, no conclusive evidence supports this practice. This study compared the efficacy and cost of prophylactic and periprocedural antibiotics in patients with EVDs.

METHODS

We reviewed the charts of 308 patients who had an EVD in place for 3 or more days between January 1996 and June 1997. Patients with EVDs placed for shunt infections or meningitis were excluded. A standard protocol was used to insert and monitor EVDs. Catheters were left in place as long as clinically indicated and changed only if they malfunctioned. Cerebrospinal fluid cultures were obtained twice weekly. Prophylactic antibiotics were used at the discretion of the attending neurosurgeon. Patients were divided into two groups: Group A comprised 209 patients who received prophylactic antibiotics for the duration of the EVD (intravenously administered cefuroxime, 1.5 g every 8 h); Group B comprised 99 patients who received only periprocedural antibiotics (intravenously administered cefuroxime, 1.5 g every 8 h, three or less doses).

RESULTS

Although there were significantly more males in Group A than in Group B, the two groups were otherwise well matched, with no significant differences in age, indications, or duration of EVD placement. The overall rate of ventriculitis was 3.9%. The infection rates for Group A (3.8%) and Group B (4.0%) were almost identical.

CONCLUSION

Prophylactic antibiotics did not significantly reduce the rate of ventriculitis in patients with EVDs, and they may select for resistant organisms. Discontinuing the use of prophylactic antibiotics for EVDs at the authors' institution would save approximately $80,000 per year in direct drug costs.
Surgical Anatomic Evaluation of the Cervical Pedicle and Adjacent Neural Structures
Authors: Uğur Hasan Çağlar , Attar Ayhan , Uz Aysun , Tekdemir İbrahim , Egemen Nihat , Çağlar Sukru , Genç Yasemin
Published: September 2004

OBJECTIVE

Although several clinical applications of transpedicular screw fixation in the cervical spine have been documented recently, few anatomic studies concerning the cervical pedicle are available. This study was designed to evaluate the anatomy and adjacent neural relationships of the middle and lower cervical pedicle (C3–C7). The main objective is to provide accurate information for transpedicular screw fixation in the cervical region and to minimize complications by providing a three-dimensional orientation.

METHODS

Twenty cadavers were used to observe the cervical pedicle and its relationships. After removal of the posterior bony elements, including spinous processes, laminae, lateral masses, and inferior and superior facets, the isthmus of the pedicle was exposed. Pedicle width, pedicle height, interpedicular distance, pedicle-inferior nerve root distance, pedicle-superior nerve root distance, pedicle-dural sac distance, medial pedicle-dural sac distance, mean angle of the pedicle, root exit angle, and nerve root diameter were measured.

RESULTS

The results indicate that there was no distance between the pedicle and the superior nerve root and between the pedicle and the dural sac in 16 specimens, whereas there was a slight distance in the lower cervical region in the 4 other specimens. The mean distance between the pedicle and the inferior nerve root for all specimens ranged from 1.0 to 2.5 mm. The mean distance between the medial pedicle and the dural sac increased consistently from 2.4 to 3.1 mm. At C3–C7, the mean pedicle height ranged from 5.2 to 8.5 mm, and the mean pedicle width ranged from 3.7 to 6.5 mm. Interpedicular distance ranged from 21.2 to 23.2 mm. The mean root exit angle ranged from 69 to 104 degrees, with the largest angle at C3 and the smallest at C6. The mean angle of the pedicle ranged from 38 to 48 degrees. The nerve root diameter increased consistently from 2.7 mm at C3 to 3.8 mm at C6 and then decreased to 3.7 mm at the C7 level. Differences in measurements were considered statistically significant at levels ranging from P < 0.05 to P < 0.01.

CONCLUSION

This study indicates that improper placement of the pedicle screw medially and superiorly in the middle and lower cervical spine should be avoided and that the anatomic variations between individuals should be established by measurement.
αvβ3 and αvβ5 Integrin Expression in Meningiomas
Authors: Bello Lorenzo , Zhang Jianping , Nikas Demetrios C. , Strasser Jon F. , Villani Roberto M. , Cheresh David A. , Carroll Rona S. , Black Peter McL.
Published: September 2004

OBJECTIVE

Integrins are emerging as alternative receptors capable of mediating several biological functions, such as cell-matrix and cell-cell adhesion, cell migration, signal transduction, and angiogenesis. Two αv integrins, i.e., αvβ3 and αvβ5, play critical roles in mediating these activities, particularly in tumors. No data are available on the expression of these integrins in meningiomas.

METHODS

Using Western blot and immunohistochemical analyses with LM609 and PG32, two monoclonal antibodies capable of recognizing the functional integrin heterodimer, we evaluated the expression of αvβ3 and αvβ5 integrins in a series of 34 meningiomas of different histological subtypes and grades. We studied their expression in tumor cells and vasculature, as well as the expression of their related angiogenic factors (fibroblast growth factor 2 and vascular endothelial growth factor) and the αvβ3 ligand vitronectin.

RESULTS

αvβ3 and αvβ5 integrins were expressed by neoplastic vasculature and cells. αvβ3 and αvβ5 expression was associated and correlated with that of their respective growth factors (fibroblast growth factor 2 and vascular endothelial growth factor) and microvessel counts and densities. αvβ3 was more strongly expressed than αvβ5 in two cases of histologically benign meningiomas with aggressive clinical behavior. αvβ3 expression was associated with that of its related ligand vitronectin and was also evident in small vessels of brain tissue closely surrounding meningiomas.

CONCLUSION

Our data demonstrate the expression of αvβ3 and αvβ5 integrins in meningioma cells and vasculature. Our findings suggest a role for both of these integrins, and particularly αvβ3, in meningioma angiogenesis.
Primary Spinal Epidural Mantle Cell Lymphoma: Case Report
Authors: Barnard Maja , Perez-Ordoñez Bayardo , Rowed David W. , Ang Lee Cyn
Published: September 2004

OBJECTIVE AND IMPORTANCE

Mantle cell lymphoma is a distinct clinicopathological type of non-Hodgkin's lymphoma that often presents at an advanced stage, with systemic spread. Spinal involvement is uncommon and generally occurs as part of advanced disease or generalized relapses. Primary spinal epidural lymphoma is a rare initial manifestation of non-Hodgkin's lymphoma, and mantle cell lymphoma with initial presentation in the spinal epidural space is extremely rare, having been previously reported in only two cases.

CLINICAL PRESENTATION

We report a case of a 71-year-old man who presented with increasing weakness and numbness of the legs. Magnetic resonance imaging revealed a spinal epidural mass in the lumbosacral region.

INTERVENTION

The patient underwent a partial L4 and L5–S1 laminectomy, with incomplete resection of the mass for spinal decompression and tissue diagnosis. Mantle cell lymphoma was diagnosed in the pathological examination.

CONCLUSION

After radiotherapy, the disease recurred with a soft-tissue mass in the anterior maxillary area of the face. The patient underwent restaging and was treated with chemotherapy, with only a partial response. Mantle cell lymphoma with primary spinal epidural presentation is rare. This diagnosis can be established and other causes of spinal cord compression can be ruled out by obtaining tissue for proper histopathological examinations. Because of its aggressive behavior and poor prognosis, mantle cell lymphoma should be treated using a combined-modality approach.
Nimodipine-induced Acute Hypoxemia: Case Report
Authors: Devlin John W. , Coplin William M. , Murry Kellie R. , Rengachary Setti S. , Wilson Robert F.
Published: September 2004

OBJECTIVE AND IMPORTANCE

Nimodipine is commonly used to improve neurological outcomes after subarachnoid hemorrhage. Although nimodipine reportedly has high specificity for the cerebral vasculature, adverse systemic effects such as hypotension have been described. This case report describes a patient with traumatic subarachnoid hemorrhage who experienced two episodes of previously undescribed, life-threatening hypoxemia that was directly related to nimodipine therapy.

CLINICAL PRESENTATION

The patient experienced acute hypoxemia (partial pressures of oxygen of 32.9 and 58.7 mm Hg), on two separate occasions (3 d apart), that was temporally related to single doses of nimodipine therapy for traumatic subarachnoid hemorrhage. Other disease- and medication-related causes did not explain these episodes.

INTERVENTION

After the inspired oxygen concentration was increased to 100% (both episodes) and the positive end expiratory pressure was increased to 7.5 mm Hg (first episode), the arterial oxygen saturation of the patient returned to baseline levels (>99%) within 40 minutes in each instance. Nimodipine therapy was discontinued after each episode.

CONCLUSION

It is hypothesized that, in the presence of concomitant adult respiratory distress syndrome, nimodipine increased ventilation/perfusion ratio mismatch, through its direct vasodilatory effects on the pulmonary artery, and possibly interfered with the reflex hypoxic pulmonary vasoconstriction necessary to maintain adequate oxygenation for this patient. Clinicians should carefully monitor the oxygenation status of patients when nimodipine therapy is initiated.
Is There a Benefit of Preoperative Meningioma Embolization?
Authors: Bendszus Martin , Rao Gerad , Burger Ralf , Schaller Carlo , Scheinemann Katrin , Warmuth-Metz Monika , Hofmann Erich , Schramm Johannes , Roosen Klaus , Solymosi Laszlo
Published: September 2004

OBJECTIVE

To evaluate the effect of preoperative embolization of meningiomas on surgery and outcomes.

METHODS

In a prospective study, 60 consecutive patients with intracranial meningiomas who were treated in two neurosurgical centers were included. In Center A, embolization was performed for none of the patients (n = 30). In Center B, 30 consecutive patients with embolized meningiomas were treated. Preoperatively, tumor size and location, neurological status, and Barthel scale score were recorded. In Center B, the extent of tumor devascularization was evaluated using angiography and postembolization magnetic resonance imaging. Intraoperatively, blood loss, the numbers of blood units transfused, and the observations of the neurosurgeon concerning hemostasis, tumor consistency, and intratumoral necrosis were recorded. Postoperatively, the neurological status and duration of hospitalization were recorded. Six months after surgery, the outcomes were assessed using the Barthel scale and neurological examinations.

RESULTS

The mean tumor sizes were 22.9 cc in Center A and 29.6 cc in Center B (P > 0.1). The mean blood losses did not differ significantly (646 ml in Center A versus 636 ml in Center B;P > 0.5). However, for a subgroup of patients with subtotal devascularization (>90% of the tumor) on postembolization magnetic resonance imaging scans in Center B, blood loss was less, compared with the entire group in Center A (P < 0.05). The observations of the neurosurgeon regarding hemostasis, tumor consistency, and intratumoral necrosis did not differ significantly. There were no surgery-related deaths in either center. The rates of surgical morbidity, with permanent neurological worsening, were 20% (n = 6) in Center A and 16% (n = 5) in Center B. There was one permanent neurological deficit (3%) caused by embolization.

CONCLUSION

In this preliminary study, only complete embolization had an effect on blood loss. The value of preoperative embolization for all meningiomas must be reconsidered, especially in view of the high costs and risks of embolization.
Effects of Timing of Coil Embolization after Aneurysmal Subarachnoid Hemorrhage on Procedural Morbidity and Outcomes
Authors: Baltsavias Gerasimos S. , Byrne James V. , Halsey Jim , Coley Stuart C. , Sohn Min-Joo , Molyneux Andrew J.
Published: September 2004

OBJECTIVE

To elucidate the effect of treatment timing on procedural clinical outcomes after aneurysmal subarachnoid hemorrhage (SAH) for patients treated by endosaccular coil embolization.

METHODS

A group of 327 patients who were consecutively treated, during a 46-month period, for ruptured intracranial aneurysms by coil embolization within 30 days after SAH were evaluated. Outcomes were assessed by comparing immediate pretreatment World Federation of Neurological Surgeons (WFNS) grades, 72-hour posttreatment WFNS grades, and modified Glasgow Outcome Scale scores at 6 months for patients treated within 48 hours (Group 1), 3 to 10 days (Group 2), or 11 to 30 days (Group 3) after SAH.

RESULTS

The three interval-to-treatment groups included 33, 38, and 29% of the patients, respectively. Before treatment, 70% of the patients in Group 1, 78% of those in Group 2, and 83% of those in Group 3 were in good clinical grades (i.e., WFNS Grade 1 or 2). After coil embolization, the WFNS grades were either unchanged or improved for 93.5% of the patients in Group 1, 89.5% of those in Group 2, and 91.5% of those in Group 3. After 6 months, 81.3% of the patients in Group 1 experienced good outcomes (modified Glasgow Outcome Scale scores of 1 or 2), as did 84% of those in Group 2 and 80% of those in Group 3. No statistical difference was demonstrated between the three groups when they were compared for these two variables.

CONCLUSION

The interval between endovascular treatment and SAH did not affect periprocedural morbidity rates or 6-month outcomes. Coil embolization should therefore be performed as early as possible after aneurysmal SAH, to prevent aneurysmal rerupture.
Results after Surgical and Endovascular Treatment of Paraclinoid Aneurysms by a Combined Neurovascular Team
Authors: Hoh Brian L. , Carter Bob S. , Budzik Ronald F. , Putman Christopher M. , Ogilvy Christopher S.
Published: September 2004

OBJECTIVE

Advances in surgical and endovascular techniques have improved treatment for paraclinoid aneurysms. A combined surgical and endovascular team can formulate individualized treatment strategies for patients with paraclinoid aneurysms. Patients who are considered to be at high surgical risk can be treated endovascularly to minimize morbidity. We reviewed the clinical and radiographic outcomes of 238 paraclinoid aneurysms treated by our combined surgical and endovascular unit.

METHODS

From 1991 to 1999, the neurovascular team treated 238 paraclinoid aneurysms in 216 patients at the Massachusetts General Hospital. The modality of treatment for each aneurysm was chosen based on anatomic and clinical risk factors, with endovascular treatment offered to patients considered to have higher surgical risks. One hundred eighty aneurysms were treated by direct surgery, 57 were treated by endovascular occlusion, and one was treated by surgical extracranial-intracranial bypass and endovascular internal carotid artery balloon occlusion. Locations were transitional, 12 (5%); carotid cave, 11 (5%); ophthalmic, 131 (55%); posterior carotid wall, 38 (16%); and superior hypophyseal 46 (19%). Lesions contained completely within the cavernous sinus were excluded from this analysis.

RESULTS

Using the Glasgow Outcome Scale (GOS), overall clinical outcomes were excellent or good (GOS 5 or 4), 86%; fair (GOS 3), 7%; poor (GOS 2), 4%; and death (GOS 1), 3%. Among the surgically treated patients, 90% experienced excellent or good outcomes (GOS 5 or 4), 6% had fair outcomes (GOS 3), 2% had poor outcomes (GOS 2), and 3% died (GOS 1). Among the endovascularly treated patients, 74% had excellent or good outcomes (GOS 5 or 4), 12% had fair outcomes (GOS 3), 10% had poor outcomes (GOS 2), and 4% died (GOS 1). The overall major and minor complication rate from surgery was 29%, with a 6% surgery-related permanent morbidity rate and a mortality rate of 0%. The overall major and minor complication rate from endovascular treatment was 21%, with a 3% endovascular-related permanent morbidity rate and a 2% mortality rate. Visual outcomes for patients who presented with visual symptoms were as follows: improved, 69%; no change, 25%; worsened, 6%; and new visual deficits, 3%. In general, angiographic efficacy was lower in the endovascular treatment group.

CONCLUSION

A combined team approach of direct surgery and endovascular coiling can lead to good outcomes in the treatment for paraclinoid aneurysms, including high-risk lesions that might not have been treated in previous surgical series.
Management and Outcomes in a Low-volume Cerebral Aneurysm Practice
Authors: Naso William B. , Rhea Andrew H. , Poole Allen
Published: September 2004

OBJECTIVE

To review management strategies, outcomes, and complications in cerebral aneurysm surgery in a low-volume aneurysm practice.

METHODS

Seventy-nine craniotomies to treat aneurysms were performed between June 1996 and November 1999. Patient management strategy is outlined, complications are assessed, and outcomes are described.

RESULTS

Twenty-six patients underwent surgery to treat unruptured aneurysms. Forty-two patients presented with Hunt and Hess Grade 1 to 3 subarachnoid hemorrhage. Eleven patients presented with Grade 4 or 5 subarachnoid hemorrhage. Twenty-four patients (92.3%) with unruptured aneurysms experienced favorable outcomes. Of the patients with unruptured anterior circulation aneurysms, 96% achieved favorable recoveries. Thirty-eight patients (90.5%) with Grade 1 to 3 subarachnoid hemorrhage experienced favorable outcomes; four of these patients were moderately disabled. Among patients with Grade 1 to 3 subarachnoid hemorrhage, the mortality rate was 7.1%. Of patients with Grade 4 or 5 subarachnoid hemorrhage, five (45.5%) experienced favorable outcomes, but four of these patients were moderately disabled; two patients (18.2%) were severely disabled, and four patients (36.4%) died.

CONCLUSION

Acceptable clinical outcomes can be achieved in lower-volume aneurysm practices. A multidisciplinary subspecialty approach with aggressive perioperative care, especially in the prevention and treatment of cerebral vasospasm, is important in obtaining these results. Close interaction with medical consultants and other subspecialists is necessary.
Transcallosal Resection of Hypothalamic Hamartomas, with Control of Seizures, in Children with Gelastic Epilepsy
Authors: Rosenfeld Jeffrey V. , Harvey A. Simon , Wrennall Jacquie , Zacharin Margaret , Berkovic Samuel F.
Published: September 2004

OBJECTIVE

Hypothalamic hamartomas (HHs) are associated with precocious puberty and gelastic epilepsy; the seizures are often refractory to antiepileptic medications and associated with delayed development and disturbed behavior. The current opinion is that surgery to treat intrahypothalamic lesions is formidable and that complete excision is not technically achievable. We report our experience with a transcallosal approach to the resection of HHs.

METHODS

Five children (age, 4–13 yr) with intractable epilepsy and HHs underwent preoperative clinical, electroencephalographic, and imaging evaluations. Two patients experienced only gelastic seizures, and three patients experienced mixed seizure disorders with drop attacks; all experienced multiple daily seizures. Patients were evaluated with respect to seizures, cognition, behavior, and endocrine status 9 to 37 months (mean, 24 mo) after surgery. The HHs were approached via a transcallosal-interforniceal route to the third ventricle and were resected using a microsurgical technique and frameless stereotaxy.

RESULTS

Complete or nearly complete (>95%) excision of the HHs was achieved for all patients, with no adverse neurological, psychological, or visual sequelae. Two patients experienced mild transient diabetes insipidus after surgery. Two patients developed appetite stimulation, but no other significant endocrinological sequelae were observed. Three patients are seizure-free and two patients have experienced only occasional, brief, mild gelastic seizures after surgery, all with reduced antiepileptic medications. On the basis of parental reports and our own subjective observations, the children also exhibited marked improvements in behavior, school performance, and quality of life.

CONCLUSION

Complete or nearly complete resection of HHs can be safely achieved via a transcallosal approach, with the possibility of seizure freedom and neurobehavioral improvements.
Recurrent Germinoma in the Optic Nerve: Report of Two Cases
Authors: Nakajima Takeshi , Kumabe Toshihiro , Jokura Hidefumi , Yoshimoto Takashi
Published: September 2004

OBJECTIVE AND IMPORTANCE

Intracranial germinomas often disseminate via the ventricular and subarachnoid pathways, but seeding to the perioptic arachnoid space is extremely unusual. We report two cases of recurrent germinoma seeding in the optic nerve.

CLINICAL PRESENTATION

Two men with pure germinoma were initially treated with three cycles of a three-drug regimen of bleomycin, etoposide, and cisplatin, and a complete response was achieved. Patient 1 experienced ventricle wall dissemination 10 months after undergoing the initial treatment and was successfully treated with three cycles of carboplatin and etoposide and then by 24-Gy whole-ventricle radiation. Twelve months later, he complained of progressive visual acuity loss, and magnetic resonance imaging demonstrated bilateral enhancement of the optic nerves. Patient 2 also experienced ventricle wall dissemination 3 months after undergoing the initial chemotherapy, but he exhibited a complete response after undergoing 24-Gy whole-ventricle radiation. Two years later, he complained of progressive visual acuity loss. Magnetic resonance imaging demonstrated bilateral enhancement of the optic nerves and cerebellar hemispheres.

INTERVENTION

None of the locations of recurrence were included in the irradiation field, whereas there was no recurrence within the radiation field. Complete responses were obtained with three cycles of a three-drug regimen of ifosfamide, cisplatin, and etoposide and then by 24-Gy whole-brain radiation that included the bilateral optic nerves. The visual acuity of each patient improved slightly.

CONCLUSION

Delayed seeding in the optic nerve may result from germinoma cells that remain dormant, so they cannot be destroyed by chemotherapy regimens alone.
Chiari Type I Malformation Presenting as Glossopharyngeal Neuralgia: Case Report
Authors: Kanpolat Yucel , Unlu Agahan , Savas Ali , Tan Funda
Published: September 2004

OBJECTIVE AND IMPORTANCE

Chiari Type I malformation is an important pathological state in which the brainstem is compressed by the cerebellar tonsil. We present a case of glossopharyngeal neuralgia caused by Chiari Type I malformation.

CLINICAL PRESENTATION

A 50-year-old male patient was admitted with glossopharyngeal neuralgia. Magnetic resonance imaging studies revealed caudal displacement of the left cerebellar tonsil.

INTERVENTION

Small occipital craniectomy and C1 laminectomy were performed. The left cerebellar tonsil was resected.

CONCLUSION

This glossopharyngeal neuralgia was caused by compression of the lower cranial nerves and brainstem by the displaced left cerebellar tonsil. Decompression and pain relief were obtained with resection of the cerebellar tonsil. The patient was pain-free 30 weeks after the operation.
Inflammation, Immunity and Vaccines for Helicobacter pylori
Authors: Del Giudice Giuseppe , Michetti Pierre
Published: September 2004

Helicobacter pylori causes chronic gastritis in the human stomach, yet only a minority of infected individuals develop peptic ulcer disease, atrophic gastritis, or gastric malignancies. The severity, progression, and consequences of H. pylori infection have been shown to depend on the host genetic background, and in particular on gene polymorphisms affecting the host immune response. Numerous studies published last year brought new information on the mechanisms by which the host genetic make‐up modifies the inflammatory and immune responses to H. pylori and the induction of tissue damage secondary to the infection. Novel insights on the regulatory role of H. pylori on the adaptive T‐cell response and on its consequences for the persistence of the infection and for the development of vaccines are discussed.
Pathogenesis of Helicobacter pylori Infection
Authors: Hofman Paul , Waidner Barbara , Hofman Véronique , Bereswill Stefan , Brest Patrick , Kist Manfred
Published: September 2004

Research in the last year has provided new insights into the function of the the cag‐associated type IV secretion system and the vacuolating toxin VacA. A quite new aspect was disclosed by the finding that Helicobacter pylori in Mongolian gerbils colonizes a very distinct topology in the gastric mucous layer, obviously providing optimal conditions for long‐term survival. Further research activities focused on H. pylori ammonia and metal metabolism as well as on bacterial stress defence mechanisms. Differential expression of approximately 7% of the bacterial genome was found at low pH suggesting that H. pylori has evolved a multitude of acid‐adaptive mechanisms. VacA was shown to interrupt phagosome maturation in macrophage cell lines as well as to modulate and interfere with T lymphocyte immunological functions. Gastric mucosa as well as the H. pylori‐infected epithelial cell line AGS strongly express IL‐8 receptor A and B, which might contribute to the augmentation of the inflammatory response. Accumulating evidence implicates genetic variation in the inflammatory response to H. pylori in the etiology of the increased risk of gastric cancer after H. pylori infection. The chronic imbalance between apoptosis and cell proliferation is the first step of gastric carcinogenesis. In this regard, it was demonstrated that coexpression of two H. pylori proteins, CagA and HspB, in AGS cells, caused an increase in E2F transcription factor, cyclin D3, and phosphorylated retinoblastoma protein.

Taken together, we now have a better understanding of the role of different virulence factors of H. pylori. There is still a lot to be learned, but the promising discoveries summarized here, demonstrate that the investigation of the bacterial survival strategies will give novel insights into pathogenesis and disease development.
Helicobacter pylori and Extragastric Diseases – Other Helicobacters
Authors: Gasbarrini Antonio , Carloni Emilia , Gasbarrini Giovanni , Chisholm Stephanie A.
Published: September 2004

Reports on Helicobacter pylori and extragastric diseases have almost doubled this year compared with last year, bearing witness to the persistent scientific interest in this branch of Helicobacter‐related pathology. Data belong increasingly to the area of vascular medicine, as well as hematology, dermatology, pediatrics and other fields. Unfortunately, these studies show overall controversial results, due to the impact of several confounding factors, and to the difficulty of recruiting homogeneous patient populations. Furthermore, many studies continue to be conducted on Helicobacter species other than H. pylori, focusing on animal models of gastroenterological illnesses which may retain strong similarities with human diseases. In this paper, taxonomy, detection and characterisation of Helicobacter spp. will be reviewed, together with the most important data issued this year on other Helicobacters and animal models.
Therapy of Helicobacter pylori
Authors: McLoughlin Ramona , Racz Istvan , Buckley Martin , O'Connor Humphrey J. , O'Morain Colm
Published: September 2004

This represents an overview of the main data published over the last year on the therapy of Helicobacter pylori. The problem of increasing failure of H. pylori eradication has been the main focus, with increasing resistance and poor patient compliance being the main culprits. Simple regimens are necessary to improve patient compliance. New antibiotics and novel agents are appraised with mixed results.
Diagnosis of Helicobacter pylori Infection
Authors: Makristathis Athanasios , Hirschl Alexander M. , Lehours Philippe , Mégraud Francis
Published: September 2004

While there are some attempts to improve culture of Helicobacter pylori, molecular methods have been the main focus of this interest. Their main application concerns the development of rapid tests also allowing the determination of bacterial resistance, i.e. real‐time polymerase chain reaction (PCR) or fluorescence in situ hybridization (FISH), or to genotype the strains. Attempts to improve, simplify or explain the discrepancies of urea breath test results have been made and new generation of stool antigen test with monoclonal antibodies either using the standard ELISA format or rapid immunoenzymatic detection have confirmed their value. With regard to serology, studies have mainly focused on the distinction of infections with more pathogenic strains and the ability to diagnose atrophic gastritis with the Gastropanel.
The Impact of Youth Unemployment Policy: A Shift of Workers into the Skilled Labour Force
Authors: Filges Trine , Larsen Birthe
Published: September 2004

Abstract.  This paper examines the impact on unemployment, wages, distribution and welfare of Youth Unemployment Programmes (YUPs). The aim of YUPs is to increase the number of young people acquiring skills and thereby reduce unemployment. We consider the assumption of a completely successful YUP, which delivers higher skills, and analyse what happens when the number of skilled workers increases relative to the number of unskilled workers. The analysis uses a search model with heterogeneous workers and jobs.
In vitro allergenicity of peanut after hydrolysis in the presence of polysaccharides
Authors: Mouécoucou J. , Frémont S. , Sanchez C. , Villaume C. , Méjean L.
Published: September 2004

Background
Peanut is a major allergenic product. Manufacturing processes used in food industries to improve the physicochemical properties of food‐based peanut (stabilization, texturization), could cause a modification of the digestibility of peanut proteins and, consequently, their allergenicity.

Objective
This study aimed at examining the influence of polysaccharides, i.e., gum arabic, low methylated pectin (LMP) and xylan, on the in vitro hydrolysis of peanut protein isolate (PPI) and the in vitro allergenicity of the digestion products.

Methods
PPI was hydrolysed during a two‐step in vitro hydrolysis by pepsin, followed by a trypsin/chymotrypsin (T/C) mixture performed in dialysis bags with molecular weight cut‐offs (MWCO) of 1000 or 8000 Da. SDS‐PAGE electrophoresis and immunoblotting were assessed on the peptic and T/C digestion products in (retentates) and out of the dialysis bags (dialysates).

Results
Hydrolysis by all of the digestive enzymes showed retention of some proteins in the dialysis bags in the presence of gum arabic and xylan. The retentates were recognized by IgG and IgE, particularly peptides <20 kDa. The IgE binding with peptides of retentate containing xylan from the dialysis bag with an MWCO of 1000 Da was reduced. The immunoreactivity of hydrolysis products in dialysates was considerably reduced by polysaccharides, regardless of the dialysis bag.

Conclusion
Reduction of PPI hydrolysis was probably due to non‐specific interactions between polysaccharides and peptides. In retentates, IgE‐binding epitopes were reduced by digestion and the presence of xylan. In dialysates, they were reduced by all of the polysaccharides. This work highlights the possibility of modulating this food allergy through optimized formulation.
CD28 and secretory immunoglobulin A‐dependent activation of eosinophils: inhibition of mediator release by the anti‐allergic drug, suplatast tosilate
Authors: Woerly G. , Decot V. , Loiseau S. , Loyens M. , Chihara J. , Ono N. , Capron M.
Published: September 2004

Background
Eosinophils are major effector cells in allergic diseases. After their recruitment to sites of inflammation, they contribute to the pathophysiology of the disease by releasing granule proteins and cytokines. Suplatast tosilate (IPD‐1151T), a new anti‐allergic agent, has shown beneficial effect in the treatment of asthma, associated with reduced bronchoalveolar lavage eosinophil infiltration and eosinophilic cationic protein (ECP) release in serum and sputum.

Objective
We investigated whether suplatast tosilate could exert direct effects on human eosinophil activation.

Methods
Eosinophils from hypereosinophilic patients or normal donors were purified by Percoll gradient and the magnetic cell separation system. Chemotaxis was studied using the Boyden chamber technique using three chemoattractants, formyl‐methionine‐leucine‐phenylalanine (fMLP), IL‐5 and eotaxin. Oxidative metabolism was determined by a luminol‐dependent chemiluminescence assay after activation with eotaxin or secretory IgA (sIgA). The release of ECP and eosinophil derived neurotoxin (EDN) was measured by radioimmunoassay and cytokine production was determined by ELISA following activation with sIgA or anti‐CD28.

Results
The chemotactic response to fMLP, IL‐5 and eotaxin was significantly inhibited by IPD‐1151T. Suplatast tosilate was partially inhibiting the release of reactive oxygen species (ROS) induced by eotaxin and sIgA. Activation by sIgA and CD28 ligation resulted in the release of ECP and EDN, which was inhibited by IPD‐1151T. Upon activation by anti‐CD28, only IL‐13 production was inhibited by IPD‐1151T, whereas release of IL‐2 and IFN‐γ was not affected. IL‐10 release induced by sIgA was also inhibited by IPD‐1151T. Additionally, the pro‐inflammatory cytokine IL‐6, which was secreted following anti‐CD28 and sIgA stimulation, was strongly inhibited by IPD‐1151T.

Conclusion
Through inhibition of chemotaxis, IPD‐1151T might limit the number of eosinophils at the inflammation site. Furthermore, it could reduce the pathological potential of eosinophils by inhibiting the release of ROS and cationic proteins, main inflammatory mediators produced by eosinophils. Moreover, the inhibition of immunoregulatory cytokines released by eosinophils could locally modify the immune response.
Interleukin‐1β attenuates endothelin B receptor‐mediated airway contractions in a murine in vitro model of asthma: roles of endothelin converting enzyme and mitogen‐activated protein kinase pathways
Authors: Zhang Y. , Adner M. , Cardell L.‐O.
Published: September 2004

Background
Asthma is a chronic airway disease, known to involve several inflammatory mediators. Little is known about how these mediators interact in order to produce or attenuate even basic features of the disease, like airway hyper‐reactivity and remodelling. Endothelin‐1 (ET‐1) and IL‐1β are two mediators suggested to play important roles in the induction of airway inflammation.

Objective
To investigate the interactions between ET‐1 and IL‐1β, using a novel in vitro model of asthma, focusing on airway smooth muscle contractility.

Methods
Isolated murine tracheal segments were cultured from 1 to 8 days in the absence and presence of IL‐1β. The subsequent contractile responses to sarafotoxin 6c (S6c) (selective agonist for ETB receptor) and sarafotoxin 6b (S6b) (ETA and ETB receptor agonist) were recorded by a myographs system. In all experiments, ETB receptors were desensitized before the contractile response to S6b was recorded. Thus, the response to S6b is only mediated by ETA receptors in the present study. The mRNA expressions for ET‐1 and endothelin (ET) receptors were quantified by real‐time PCR.

Results
Organ culture in the presence of IL‐1β attenuated the maximal contraction induced by S6c, but not S6b. This reduction was concentration‐dependent and was significant after 2, 4 and 8 days of culture. To investigate the mechanisms behind this, inhibitors for endothelin converting enzyme (ECE) phosphoramidon, c‐JUN N‐terminal kinase (JNK) SP600125, extracellular‐signal‐regulated kinase 1/2(ERK 1/2) PD98059 and p38 pathway SB203580 were used. Individually, SP600125 and PD98059, but not SB203580, could partly reverse the reduction induced by IL‐1β. An additional effect was obtained when SP600125 and PD98059 were combined. The mRNA expressions for ET‐1 and ETB receptor were up‐ and down‐regulated, respectively, by IL‐1β.

Conclusion
Presence of IL‐1β in the airways attenuate the contractile response mediated via ETB receptors, an effect dependent on ECE, JNK and ERK 1/2 pathways.
Effect of montelukast compared with inhaled fluticasone on airway inflammation
Authors: Overbeek S. E. , O'Sullivan S. , Leman K. , Mulder P. G. H. , Hoogsteden H. C. , Prins J.‐B.
Published: September 2004

Background
Inhaled corticosteroids are currently regarded as the gold standard in anti‐inflammatory therapy, however, leukotriene receptor antagonists have been ascribed anti‐inflammatory properties.

Objective
We directly compared the anti‐inflammatory effects of inhaled fluticasone propionate (FP, 100 μg Diskus, twice daily) and oral montelukast (MON 10 mg, nocte) in bronchial biopsies of patients with asthma in a double‐blind, double‐dummy, parallel‐group design.

Methods
Bronchial biopsies, serum and urine samples were collected from 36 atopic asthmatics before and after 8 weeks of treatment. Activated T cells (CD25+), eosinophils (MBP+) and mast cells (tryptase+) were analysed by immunohistochemistry. Serum eosinophil cationic protein (ECP) and IL‐5 were analysed by radio and enzyme immunoassay (EIA), respectively. Urinary 9α‐11β‐PGF2 and leukotriene E4 (LTE4) were measured by EIA.

Results
A comparison of changes from baseline [FP/MON ratio (95% confidence interval)] of activated T cells was not different when subjects were treated with FP compared to treatment with MON [1.00 (0.18–4.86); P=0.924]. Following treatment, mast cells in the FP group were significantly lower than in the group treated with MON [0.39 (0.16–0.97); P=0.041]. There was no difference in the number of eosinophils in the lamina propria following either treatment [0.54 (0.05–2.57); P=0.263]. However, treatment with FP resulted in a significantly greater decrease in serum ECP, compared to treatment with MON [0.37 (0.25–0.71); P=0.002].

Conclusions
FP appears to be superior to MON as an anti‐inflammatory therapy in mild asthmatics.
Prior Bordetella pertussis infection modulates allergen priming and the severity of airway pathology in a murine model of allergic asthma
Authors: Ennis D. P. , Cassidy J. P. , Mahon B. P.
Published: September 2004

Background
It has been proposed that T helper (Th)2‐driven immune deviation in early life can be countered by Th1 inducing childhood infections and that such counter‐regulation can protect against allergic asthma.

Objective
To test whether Th1‐inducing infection with Bordetella pertussis protects against allergic asthma using well‐characterized murine models.

Methods
Groups of mice were sensitized to ovalbumin (OVA) in the presence or absence of B. pertussis, a well‐characterized Th1 inducing respiratory infection. Immunological, pathological and physiological parameters were measured to assess the impact of infection on immune deviation and airway function.

Results
We demonstrate that OVA sensitization does not affect the development of B. pertussis‐specific immune responses dominated by IgG2a and IFN‐γ and does not impair Th1‐mediated clearance of airway infection. In contrast, B. pertussis infection at the time of sensitization modulated the response to OVA and significantly reduced total serum and OVA‐specific IgE. The pattern of cytokine responses, in particular OVA‐specific IL‐5 responses in the spleen was also modulated. However, B. pertussis did not cause global suppression as IL‐10 and IL‐13 levels were enhanced in OVA‐stimulated spleen cell cultures and in lavage fluid from infected co‐sensitized mice. Histopathological examination revealed that B. pertussis infection prior to OVA sensitization resulted in increased inflammation of bronchiolar walls with accompanying hyperplasia and mucous metaplasia of lining epithelia. These pathological changes were accompanied by increased bronchial hyper‐reactivity to methacholine exposure.

Conclusion
Contrary to the above premise, a Th1 response induced by a common childhood infection does not protect against bronchial hyper‐reactivity, but rather exacerbates the allergic asthmatic response, despite modulation of immune mediators.
Differential effect of mattress covers on the level of Der p 1 and Der f 1 in dust
Authors: Tempels‐Pavlica Ž. , Oosting A. J. , Terreehorst I. , Van Wijk R. Gerth , Bruijnzeel‐Koomen C. A. F. M. , De Monchy J. G. R. , Aalberse R. C.
Published: September 2004

Background
Exposure to house dust mite (HDM) allergens can lead to the development of allergic complaints. Mattress covers seem to be an obvious option for lowering allergen exposure in sensitized individuals. Previous studies have shown that Dermatophagoides pteronissinus was the most prevalent HDM species in the Netherlands.

Objective
In the present study, we investigated the effect of mattress covers on Der p 1 and Der f 1 concentrations in dust samples in three areas in the Netherlands; Groningen, Utrecht and Rotterdam.

Methods
Dust was obtained from mattresses of 277 patients at the beginning of the study and after 12 months of the placebo‐controlled intervention. It was analysed for allergen content by immunoassay. The differential effect of the intervention on Der p 1 vs. Der f 1 was analysed in a subgroup with Der p 1+Der f 1>1 μg/g dust (N=161). It was tested whether the intervention caused a significant change in the Der f 1/Der p 1 ratio.

Results
At t=0 we found very similar levels of the group 1 allergens of both species. The relatively high prevalence of D. farinae in our study was geographically restricted: the median Der f 1/Der p 1 ratio was 11.1 in the Rotterdam area compared with 1.32 in the Utrecht area and 0.33 in the Groningen area. Analysis of our data showed that the favourable intervention effect found for the combined allergen data (reduction factor=2.9, P<0.001) is essentially due to a favourable effect of the intervention on the Der f 1 levels only (reduction factor=3.6, P<0.001). The effect on the Der p 1 level was remarkably small (reduction factor: 1.2, P=0.48). In the intervention group, the Der f 1/Der p 1 ratio decreased after 12 months by a factor 2.0, whereas in the placebo group it increased (probability of the intervention effect: P<0.005).

Conclusion
Mite‐impermeable covers are more effective in reducing the level of Der f 1 than that of Der p 1.