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1.
Eur Spine J ; 26(8): 2204-2210, 2017 08.
Article in English | MEDLINE | ID: mdl-28688061

ABSTRACT

STUDY DESIGN: Technical note. OBJECTIVE: We describe a novel technique of bilateral longitudinal sacral osteotomy allowing direct reduction of high pelvic incidence (PI) and correction of sagittal imbalance. METHODS: A 25-year-old female patient presented with a disabling lumbo-sacral kyphosis fused in situ through previous operations with residual low-grade wound infection and grade IV L5/S1 spondylolisthesis with severity index (SI) of 65%. A two-stage correction was performed. First anterior in situ fixation of the L4-L5-S1 segments was performed using a hollow modular anchorages (HMA) screw and L3/L4 anterior interbody cage. The second stage consisted of instrumentation of the lower lumbar spine and pelvis; placement of an S1 transverse K-wire as pivot point and bilateral longitudinal sacral osteotomy which allowed for gradual retroversion of the central sacrum relative to the pelvis. RESULTS: Sacrum was derotated by 30° which allowed to restore spinal sagittal balance and decrease SI by 15%. Postoperative recovery was complicated by a flare up of the pre-existing deep wound infection. CONCLUSIONS: Bilateral longitudinal sacral osteotomy appears to be a safe and efficient way of correcting the sagittal imbalance caused by an extremely high PI. Although technically demanding, it achieves good radiological and functional outcomes and avoids entering the spinal canal.


Subject(s)
Kyphosis/surgery , Lumbar Vertebrae/surgery , Osteotomy/methods , Pelvis/pathology , Sacrum/surgery , Spinal Fusion/methods , Adult , Female , Humans , Kyphosis/pathology
2.
J Clin Endocrinol Metab ; 98(12): E1918-26, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24152687

ABSTRACT

CONTEXT: Targeted secretion inhibitors (TSIs), a new class of recombinant biotherapeutic proteins engineered from botulinum toxin, represent a novel approach for treating diseases with excess secretion. They inhibit hormone secretion from targeted cell types through cleavage of SNARE (soluble N-ethylmaleimide-sensitive factor-activating protein receptor) proteins. qGHRH-LH(N)/D is a TSI targeting pituitary somatotroph through binding to the GHRH-receptor and cleavage of the vesicle-associated membrane protein (VAMP) family of SNARE proteins. OBJECTIVE: Our objective was to study SNARE protein expression in pituitary adenomas and to inhibit GH secretion from somatotropinomas using qGHRH-LH(N)/D. DESIGN: We analyzed human pituitary adenoma analysis for SNARE expression and response to qGHRH-LH(N)/D treatment. SETTING: The study was conducted in University Hospitals. PATIENTS: We used pituitary adenoma samples from 25 acromegaly and 47 nonfunctioning pituitary adenoma patients. OUTCOME: Vesicle-SNARE (VAMP1-3), target-SNARE (syntaxin1, SNAP-23, and SNAP-25), and GHRH-receptor detection with RT-qPCR, immunocytochemistry, and immunoblotting. Assessment of TSI catalytic activity on VAMPs and release of GH from adenoma cells. RESULTS: SNARE proteins were variably expressed in pituitary samples. In vitro evidence using recombinant GFP-VAMP2&3 or pituitary adenoma lysates suggested sufficient catalytic activity of qGHRH-LH(N)/D to degrade VAMPs, but was unable to inhibit GH secretion in somatotropinoma cell cultures. CONCLUSIONS: SNARE proteins are present in human pituitary somatotroph adenomas that can be targeted by TSIs to inhibit GH secretion. qGHRH-LH(N)/D was unable to inhibit GH secretion from human somatotroph adenoma cells. Further studies are required to understand how the SNARE proteins drive GH secretion in human somatotrophs to allow the development of novel TSIs with a potential therapeutic benefit.


Subject(s)
Adenoma/drug therapy , Antineoplastic Agents/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Growth Hormone-Secreting Pituitary Adenoma/drug therapy , Neoplasm Proteins/antagonists & inhibitors , Pituitary Gland/drug effects , SNARE Proteins/antagonists & inhibitors , Secretory Pathway/drug effects , Acromegaly/etiology , Acromegaly/prevention & control , Adenoma/metabolism , Adenoma/pathology , Antineoplastic Agents/chemistry , Botulinum Toxins/chemistry , Botulinum Toxins/genetics , Botulinum Toxins/pharmacology , Drug Design , Growth Hormone-Releasing Hormone/analogs & derivatives , Growth Hormone-Releasing Hormone/genetics , Growth Hormone-Releasing Hormone/metabolism , Growth Hormone-Releasing Hormone/pharmacology , Growth Hormone-Secreting Pituitary Adenoma/metabolism , Growth Hormone-Secreting Pituitary Adenoma/pathology , Human Growth Hormone/antagonists & inhibitors , Human Growth Hormone/genetics , Human Growth Hormone/metabolism , Humans , Ligands , Molecular Targeted Therapy , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Pituitary Gland/metabolism , Pituitary Gland/pathology , Pituitary Neoplasms/drug therapy , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/pathology , Protein Engineering , Protein Structure, Tertiary , Receptors, LHRH/antagonists & inhibitors , Receptors, LHRH/genetics , Receptors, LHRH/metabolism , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/pharmacology , SNARE Proteins/genetics , SNARE Proteins/metabolism , Tumor Cells, Cultured
3.
Neurol Neurochir Pol ; 39(3): 220-4; discussion 225, 2005.
Article in Polish | MEDLINE | ID: mdl-15981160

ABSTRACT

BACKGROUND AND PURPOSE: The aim of this paper is to present an alternative method of cranioplasty with the use of an autologous cranial bone flap stored between primary and restorative surgery in the subcutaneous pocket in the lateral hypogastric region. MATERIAL AND METHODS: Between January 1999 and April 2002, in the Department of Neurosurgery of Medical University of Lódz we performed 36 procedures of the bone flap implantation into the abdominal subcutaneous fat tissue. These procedures followed craniectomy, mainly in cases of acute subdural hematomas and ruptured intracranial aneurysms. RESULTS: After storage, the bone flap was reimplanted in 28 patients. The mean time between operations was 14 days (range 8-53 days). In the cranioplasty group we had only one infection of the bone flap. Among patients excluded from the bone flap restoration we observed one inflammatory complication in the abdominal wall and one subcutaneous hematoma requiring evacuation. CONCLUSIONS: In our opinion, the presented method of the cranial defect's supplementation may be competitive to procedures utilizing synthetic prostheses in the population of patients for whom reimplantation of the bone flap will be expected in 2-3 months after the primary operation. Advantages of the procedure are: the autologous bone graft, the excellent cosmetic effect, low costs of the procedure and low rate of inflammatory complications.


Subject(s)
Abdominal Wall/surgery , Bone Regeneration , Bone Transplantation/methods , Craniotomy/methods , Surgical Flaps , Abdominal Wall/pathology , Adult , Aged , Female , Hematoma, Subdural, Acute/surgery , Humans , Intracranial Aneurysm/surgery , Male , Middle Aged , Poland , Retrospective Studies , Time Factors , Transplantation, Autologous
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