Diameters and bone thickness at the margin of the foramen magnum in dry skulls from pediatric population: a cross-sectional anatomical study.

PURPOSE: The purpose of the study was to estimate the size and bone thickness at the margin of the foramen magnum in a pediatric population. METHODS: Sixty occipital bone specimens from the collection of macerated skulls at the Department of Anatomy, University of Zagreb, were examined and measured using a vernier scale/caliper. For the purpose of analysis, specimens were divided into two age groups: 1-6 years and 7-18 years of age (before and after the fusion of ossification centers in the occipital bone). We measured the following: antero-posterior and transverse diameters of the foramen magnum, bone thicknesses at the basion, opisthion, two paramedial points on the anterior and posterior margins, and at the occipito-squamous junction. RESULTS: Data presented in this study show that diameters of the foramen magnum increase with age, whereas bone thickness shows variable behavior depending on the measured area. CONCLUSIONS: Increases in diameters in specimens from the younger age group and their absence in specimens from older subjects reflect the growth pattern of the basilar part of occipital bone. Variability of bone thickness at the margin of the foramen magnum and lack of its association with age of the subjects may be attributed to various factors and may potentially affect the clinical presentation of compression syndromes at the level of foramen magnum.

Influence of congenital central nervous system malformations on postoperative complications following placement of cerebrospinal fluid shunts in pediatric and adolescent patients.

BACKGROUND: This retrospective study was designed to evaluate whether patients with hydrocephalus associated with central nervous system (CNS) anomalies, compared with patients with hydrocephalus and absent CNS anomalies, present with significantly higher rate of postoperative complications, including more serious clinical presentation, increased life threat, and higher postoperative or late mortality rate. METHODS: We performed a retrospective study using medical records of 100 patients of pediatric and adolescent age (0-18 years) between 2004 and 2010 treated with operative cerebrospinal fluid (CSF) shunt placement. RESULTS: In both groups of patients, there were 43 postoperative complications, including 12 mechanical obstructions of the CSF drainage systems, 13 disconnections, 11 dislocations of proximal catheter, 6 inflammatory complications (meningitis), and 1 latex allergy. Patients with hydrocephalus associated with CNS anomalies were presented with statistically higher rate of postoperative complications (U = 303.5, z = -3.27, p = 0.001), higher number of operations, at least one complication more per patient, more complicated clinical course, higher life threat, and higher late mortality rate. CONCLUSIONS: After installing the CSF drain system, children and adolescents with hydrocephalus associated with anomalies of the CNS require regular and careful follow-up.

Pseudocholinesterase activity in cerebrospinal fluid as a biomarker of solid central nervous system tumors in children.

AIM: To determine the activity of pseudocholinesterase (PChE) in cerebrospinal fluid (CSF) and serum in children with solid central nervous system (CNS) tumor and to assess whether PChE activity could be a valid biomarker for solid CNS tumors in children. METHODS: The study and control group included 30 children each. Children in the study group had a solid CNS tumor, while those from the control group had never suffered from any tumor diseases. CSF and serum samples were collected from all participants and PChE activity was determined using the Ellman's spectrophotometric method. PChE activity in CSF was shown as a cerebrospinal fluid/serum ratio expressed in percentage, ie, PChE CSF/serum ratio. Receiver operating characteristic (ROC) curve was used to assess whether PChE activity can be used as a biomarker for identifying children with solid CNS tumors. RESULTS: Children with solid CNS tumor had significantly higher PChE activity in CSF and serum, as well as PChE CSF/serum ratio (P=0.001). PChE CSF/serum ratio in the study group was 2.38% (interquartile range [IQR] 1.14-3.97) and 1.09% (IQR 0.95-1.45) in the control group. ROC curve analysis of PChE CSF/serum ratio resulted in an area under the curve (AUC) value of 0.76 (95% confidence interval [CI] 0.63-0.88) and a cut-off of 1.09. Twenty five of 29 patients with elevated PChE CSF/serum ratio had a tumor, corresponding to a sensitivity of 83% and a specificity of 53%. CONCLUSION: PChE CSF/serum ratio may be used as a test or biomarker with good sensitivity for solid CNS tumors in children.

Pentadecapeptide BPC 157 and its effects on a NSAID toxicity model: diclofenac-induced gastrointestinal, liver, and encephalopathy lesions.

AIMS: We attempted to fully antagonize the extensive toxicity caused by NSAIDs (using diclofenac as a prototype). MAIN METHODS: Herein, we used the stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419), an anti-ulcer peptide shown to be efficient in inflammatory bowel disease clinical trials (PL 14736) and various wound treatments with no toxicity reported. This peptide was given to antagonize combined gastrointestinal, liver, and brain toxicity induced by diclofenac (12.5mg/kg intraperitoneally, once daily for 3 days) in rats. KEY FINDINGS: Already considered a drug that can reverse the toxic side effects of NSAIDs, BPC 157 (10 µg/kg, 10 ng/kg) was strongly effective throughout the entire experiment when given (i) intraperitoneally immediately after diclofenac or (ii) per-orally in drinking water (0.16 µg/mL, 0.16 ng/mL). Without BPC 157 treatment, at 3h following the last diclofenac challenge, we encountered a complex deleterious circuit of diclofenac toxicity characterized by severe gastric, intestinal and liver lesions, increased bilirubin, aspartate transaminase (AST), alanine transaminase (ALT) serum values, increased liver weight, prolonged sedation/unconsciousness (after any diclofenac challenge) and finally hepatic encephalopathy (brain edema particularly located in the cerebral cortex and cerebellum, more in white than in gray matter, damaged red neurons, particularly in the cerebral cortex and cerebellar nuclei, Purkinje cells and less commonly in the hippocampal neurons). SIGNIFICANCE: The very extensive antagonization of diclofenac toxicity achieved with BPC 157 (µg-/ng-regimen, intraperitoneally, per-orally) may encourage its further use as a therapy to counteract diclofenac- and other NSAID-induced toxicity.

Peptide therapy with pentadecapeptide BPC 157 in traumatic nerve injury.

We focused on the healing of rat transected sciatic nerve and improvement made by stable gastric pentadecapeptide BPC 157 (10 microg, 10ng/kg) applied shortly after injury (i) intraperitoneally/intragastrically/locally, at the site of anastomosis, or after (ii) non-anastomozed nerve tubing (7 mm nerve segment resected) directly into the tube. Improvement was shown clinically (autotomy), microscopically/morphometrically and functionally (EMG, one or two months post-injury, walking recovery (sciatic functional index (SFI)) at weekly intervals). BPC 157-rats exhibited faster axonal regeneration: histomorphometrically (improved presentation of neural fascicles, homogeneous regeneration pattern, increased density and size of regenerative fibers, existence of epineural and perineural regeneration, uniform target orientation of regenerative fibers, and higher proportion of neural vs. connective tissue, all fascicles in each nerve showed increased diameter of myelinated fibers, thickness of myelin sheet, number of myelinated fibers per area and myelinated fibers as a percentage of the nerve transected area and the increased blood vessels presentation), electrophysiologically (increased motor action potentials), functionally (improved SFI), the autotomy absent. Thus, BPC 157 markedly improved rat sciatic nerve healing.

Traumatic brain injury in mice and pentadecapeptide BPC 157 effect.

Gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, an anti-ulcer peptide, efficient in inflammatory bowel disease trials (PL 14736), no toxicity reported, improved muscle crush injury. After an induced traumatic brain injury (TBI) in mice by a falling weight, BPC 157 regimens (10.0microg, 10.0ng/kgi.p.) demonstrated a marked attenuation of damage with an improved early outcome and a minimal postponed mortality throughout a 24h post-injury period. Ultimately, the traumatic lesions (subarachnoidal and intraventricular haemorrhage, brain laceration, haemorrhagic laceration) were less intense and consecutive brain edema had considerably improved. Given prophylactically (30 min before TBI) the improved conscious/unconscious/death ratio in TBI-mice was after force impulses of 0.068 Ns, 0.093 Ns, 0.113 Ns, 0.130 Ns, 0.145 Ns, and 0.159 Ns. Counteraction (with a reduction of unconsciousness, lower mortality) with both microg- and ng-regimens included the force impulses of 0.068-0.145 Ns. A higher regimen presented effectiveness also against the maximal force impulse (0.159 Ns). Furthermore, BPC 157 application immediately prior to injury was beneficial in mice subjected to force impulses of 0.093 Ns-TBI. For a more severe force impulse (0.130 Ns, 0.145 Ns, or 0159 Ns), the time-relation to improve the conscious/unconscious/death ratio was: 5 min (0.130 Ns-TBI), 20 min (0.145 Ns-TBI) or 30 min (0.159 Ns-TBI).

Different effect of antiulcer agents on rat cysteamine-induced duodenal ulcer after sialoadenectomy, but not gastrectomy.

The focus was on salivary glands in cysteamine-induced duodenal ulcer and the different effects of antiulcer agents on cysteamine-induced duodenal ulcer in sialoadenectomized but not gastrectomized rats. We tested antiulcer agents on cysteamine-induced duodenal ulcer in rats (agents/kg i.p.) simultaneously with cysteamine 400 mg/kg s.c., rat killed 24 h thereafter subjected to no surgery (normal), to gastrectomy (24 h before) or sialoadenectomy, acute (24 h before) or chronic (21 days before). (i) Ulcerogenesis: cysteamine-induced duodenal ulcer had the same severity and incidence in normal, gastrectomized or acutely or chronically sialoadenectomized rats. (ii) Antiulcer effect under normal conditions or following gastrectomy: in normal or gastrectomized rats all agents tested, gastric pentadecapeptide BPC 157 [currently in clinical trials for inflammatory bowel disease (PL-10, PLD-116, PL-14736, Pliva) (10.0 microg or 10.0 ng), ranitidine (10 mg), atropine (10 mg), omeprazole (10 mg)] inhibited cysteamine-induced duodenal ulcers, acting through gastric acid-independent mechanisms. Following sialoadenectomy, acute or chronic: ranitidine, omeprazole and atropine were completely ineffective, while pentadecapeptide BPC 157 could protect. Thus, we found that contrary to stomach, salivary glands are implicated in cytoprotective agent activity (standard agents were ineffective after sialoadenectomy). Also, gastric pentadecapeptide BPC 157 was consistently associated with a cytoprotective effect, suggesting a beneficial activity distinctive from that of H2-receptor blockers, proton-pump inhibitors and anticholinergics; but probably replacing missing salivary glands factors.