Interrelationship of cartilage composition and chondrocyte mechanics after a partial meniscectomy in the rabbit knee joint - Experimental and numerical analysis.

Site-specific and depth-dependent properties of cartilage were implemented within a finite element (FE) model to determine if compositional or structural changes in the tissue could explain site-specific alterations of chondrocyte deformations due to cartilage loading in rabbit knee joints 3 days after a partial meniscectomy (PM). Depth-dependent proteoglycan (PG) content, collagen content and collagen orientation in the cartilage extracellular matrix (ECM), and PG content in the pericellular matrix (PCM) were assessed with microscopic and spectroscopic methods. Patellar, femoral groove and samples from both the lateral and medial compartments of the femoral condyle and tibial plateau were extracted from healthy controls and from the partial meniscectomy group. For both groups and each knee joint site, axisymmetric FE models with measured properties were generated. Experimental cartilage loading was applied in the simulations and chondrocyte volumes were compared to the experimental values. ECM and PCM PG loss occurred within the superficial cartilage layer in the PM group at all locations, except in the lateral tibial plateau. Collagen content and orientation were not significantly altered due to the PM. The FE simulations predicted similar chondrocyte volume changes and group differences as obtained experimentally. Loss of PCM fixed charge density (FCD) decreased cell volume loss, as observed in the medial femur and medial tibia, whereas loss of ECM FCD increased cell volume loss, as seen in the patella, femoral groove and lateral femur. The model outcome, cell volume change, was also sensitive to applied tissue geometry, collagen fibril orientation and loading conditions.

Composition, structure and tensile biomechanical properties of equine articular cartilage during growth and maturation.

Articular cartilage undergoes structural and biochemical changes during maturation, but the knowledge on how these changes relate to articular cartilage function at different stages of maturation is lacking. Equine articular cartilage samples of four different maturation levels (newborn, 5-month-old, 11-month-old and adult) were collected (N = 25). Biomechanical tensile testing, Fourier transform infrared microspectroscopy (FTIR-MS) and polarized light microscopy were used to study the tensile, biochemical and structural properties of articular cartilage, respectively. The tensile modulus was highest and the breaking energy lowest in the newborn group. The collagen and the proteoglycan contents increased with age. The collagen orientation developed with age into an arcade-like orientation. The collagen content, proteoglycan content, and collagen orientation were important predictors of the tensile modulus (p < 0.05 in multivariable regression) and correlated significantly also with the breaking energy (p < 0.05 in multivariable regression). Partial least squares regression analysis of FTIR-MS data provided accurate predictions for the tensile modulus (r = 0.79) and the breaking energy (r = 0.65). To conclude, the composition and structure of equine articular cartilage undergoes changes with depth that alter functional properties during maturation, with the typical properties of mature tissue reached at the age of 5-11 months.

Traumatic cervical spinal cord injury: a prospective clinical study of laryngeal penetration and aspiration.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: Dysphagia is a relatively common secondary complication in patients with traumatic cervical spinal cord injuries (TCSCI). The purpose of this study was to determine the incidence of aspiration and penetration in patients with acute TCSCI. SETTING: Tampere University Hospital, Tampere, Finland. METHODS: A total of 46 patients with TCSCI were evaluated with a videofluoroscopic swallowing study (VFSS). Rosenbek's penetration-aspiration scale (PAS) was used to classify the degree of penetration or aspiration. The medical records of each patient were systematically reviewed. RESULTS: Of the 46 patients, 85% were male. The mean age at the time of the injury was 62.1 years. Most patients had an incomplete injury (78%), and most of them due to a fall (78%). In the VFSS 19 (41%) patients penetrated and 15 (33%) aspirated. Only 12 (26%) of the patients had a PAS score of 1 indicating that swallowed material did not enter the airway. Of the patients who aspirated, 73% had silent aspiration. CONCLUSION: The incidence of penetration or aspiration according to VFSS is high in this cohort of patients with TCSCI. Therefore, the swallowing function of patients with acute TCSCI should be routinely evaluated before initiating oral feeding. VFSS is highly recommended, particularly to rule out the possibility of silent aspiration and to achieve information on safe nutrition consistency.

Early in situ changes in chondrocyte biomechanical responses due to a partial meniscectomy in the lateral compartment of the mature rabbit knee joint.

We determined the biomechanical responses of chondrocytes to indentation at specific locations within the superficial zone of cartilage (i.e. patellar, femoral groove, femoral condylar and tibial plateau sites) taken from female New Zealand white rabbits three days after a partial meniscectomy in the lateral compartment of a knee joint. Confocal laser scanning microscopy combined with a custom indentation system was utilized to image chondrocyte responses at sites taken from ten contralateral and experimental knee joints. Cell volume, height, width and depth changes, global, local axial and transverse strains and Young׳s moduli were determined. Histological assessment was performed and proteoglycan content from the superficial zone of each site was determined. Relative to contralateral group cells, patellar, femoral groove and lateral femoral condyle cells in the experimental group underwent greater volume decreases (p < 0.05), due to smaller lateral expansions (with greater decreases in cell height only for the lateral femoral condyle cells; p < 0.05) whereas medial femoral and medial tibial plateau cells underwent smaller volume decreases (p < 0.05), due to less deformation in cell height (p < 0.05). Proteoglycan content was reduced in the patellar (p > 0.05), femoral groove, medial femoral condyle and medial tibial plateau experimental sites (p < 0.05). The findings suggest: (i) cell biomechanical responses to cartilage loading in the rabbit knee joint can become altered as early as 3 days after a partial meniscectomy, (ii) are site-specific, and (iii) occur before alterations in tissue mechanics or changes detectable with histology.

Site-specific cell-tissue interactions in rabbit knee joint articular cartilage.

Relationships between cartilage structure and superficial in situ chondrocyte deformations were investigated from 6 different knee joint locations (n=10 knees). Depth dependent cartilage structure and composition were quantified with microscopic/microspectroscopic methods. Medial tibial cartilages had the lowest superficial collagen content, highest collagen orientation angle, and highest proteoglycan content in the pericellular matrix relative to that in the extracellular matrix, coupled with the largest chondrocyte deformations. In contrast, femoral groove and lateral tibial cartilages had the highest superficial collagen contents, lowest collagen orientation angles, and low normalized proteoglycan contents in the pericellular matrix, coupled with the smallest chondrocyte deformations. To study cell-tissue interactions further, observations (n=57) from all locations were pooled and a multivariable linear regression was performed. Cell width deformations (R2=0.57) correlated with collagen orientation angle (standardized regression coefficient ß=0.398) and collagen content (ß=-0.402). Cell height deformations (R2=0.52) also correlated with collagen orientation (ß=-0.248) and collagen content (ß=0.455). Cell volume change upon cartilage compression (R2=0.41) correlated with collagen content (ß=0.435) and proteoglycan content (ß=0.279). In conclusion, higher collagen and proteoglycan contents combined with lower collagen orientation angle in the extracellular matrix were related to reductions in superficial chondrocyte deformations. Also, a steep gradient of proteoglycan content from the extracellular to the pericellular matrix was associated with increased cell deformation, particularly in the medial tibial plateau cartilage.

Site-dependent biomechanical responses of chondrocytes in the rabbit knee joint.

Biomechanical responses of chondrocytes were determined in specific locations within the superficial zone of patellar, femoral groove, femoral condyle and tibial plateau cartilages obtained from female New Zealand White rabbits. A confocal laser scanning microscope combined with a custom indentation system was utilized for experimentation. Changes in cell volumes and dimensions (i.e. cell height, width and depth) due to loading, global, local axial and transverse strains were determined for each site. Tissue composition and structure was analysed at each indentation site with digital densitometry, polarized light microscopy and Fourier transform infrared imaging spectroscopy. Patellar cells underwent greater volume decreases (compared to femoral groove cells; p<0.05) primarily due to greater decreases in cell height (p<0.05), consistent with greater levels of both global and local axial strains (p<0.05). Lateral condyle cells underwent greater volume decreases (compared to lateral plateau cells; p<0.05) primarily due to greater decreases in cell height, consistent with greater levels of tissue strains (p<0.05). Medial condyle cells underwent smaller volume decreases (compared to medial plateau cells; p<0.05) primarily due to elevated cell expansions in the depth direction, which was consistent with greater levels of minor transverse strains (p<0.05). Site-dependent differences in collagen orientation angles agreed conceptually with the observed cell dimensional changes. Chondrocyte biomechanical responses were highly site-dependent and corresponded primarily with the orientation of the collagen fibrils. The observed differences were thought to be due to the different biomechanical loading conditions at each site.

Chronic subdural haematoma after endoscopic treatment of a supracellar arachnoid cyst.

Neuroendoscopy is considered a safe treatment option for intracranial arachnoid cysts. However a variety of complications has been reported after such interventions. Here we present the first case of a chronic subdural hematoma two months after the combined treatment of a supracellar arachnoid cyst with endoscopic third ventriculostomy and cyst fenestration.

Fatal inhalation injury caused by airway fire during tracheostomy.

A 45-year-old man needed emergency tracheostomy and cranioplasty. He was intubated with a cuffed oral polyvinylchloride endotracheal tube and ventilated with 100% oxygen before tracheal incision. During opening of the trachea using diathermy, a popping sound was heard and flames originating from the tracheal incision were observed. The endotracheal tube was charred and its lumen had melted. Immediately after the incident, bronchofibroscopic examination revealed inhalation injury. After remaining for 8 weeks in hospital, the patient was transferred to a health care centre, where he was found dead in his bed.

Castleman's disease of the leptomeninges--immunohistochemical findings in 2 cases.

OBJECTIVE: Castleman's disease is an uncommon benign lymphoproliferative disorder that arises in lymph nodes. Few cases of Castleman's disease affecting the central nervous system have been described. CASE HISTORY: We report 2 new cases of Castleman's disease confined solely to the leptomeninges. The patients were referred to neurosurgery with presumptive clinical diagnosis of meningiomas. Histological investigation of the operative specimens taken from the abnormal leptomeninges revealed nodular lymphoid areas with multiple germinal centers surrounded by concentrically layered proliferations of small lymphocytes. Histologically, these 2 cases fulfilled the classification criteria for the mixed and for the hyaline-vascular type of Castleman's disease. The immunohistochemical analysis revealed a polyclonal B cell proliferation in the lesions with perifollicular T cell proliferation with the T helper cell predominance. CONCLUSIONS: The authors conclude that Castleman's disease involving the leptomeninges have a similar immunological pattern reported for the disease in extracranial locations and that, though being rare, Castleman's disease should be considered as a differential diagnosis when dealing with mass lesions of leptomeninges.

Evidence for excess long-term mortality after treated subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The purpose of this study was to examine the long-term mortality rate of patients with aneurysmal subarachnoid hemorrhage (SAH) compared with that of the general population. METHODS: Aneurysmal SAH patients who were treated for ruptured aneurysm from 1977 through 1998 in a tertiary referral center (n=1537) were followed up for a median of 7.5 years. Dates and causes of death were determined. Standardized mortality ratios (observed/expected deaths) according to age, sex, and Glasgow Outcome Scale at 12 months after surgery were calculated. RESULTS: The mortality rate among patients with good recovery at 12 months was twice that of the general population. The excess mortality appeared to be most evident in younger age groups. Cerebrovascular and cardiovascular diseases were the principal causes of premature death. The result was similar among patients without preexisting cardiovascular diseases at the time of SAH. CONCLUSIONS: Aneurysmal SAH patients have an excess mortality rate even after successful treatment of ruptured aneurysms. Therefore, aneurysmal SAH should be viewed more as one aspect of a chronic general vascular disease, and more attention should be given to treatment of risk factors and long-term follow-up of these patients.

Genetic analysis of MMP3, MMP9, and PAI-1 in Finnish patients with abdominal aortic or intracranial aneurysms.

MMP3, MMP9, and PAI-1 are present at increased levels in abdominal aortic aneurysms (AAAs). The promoters of these genes contain polymorphisms, with alleles that exhibit different transcriptional activities in vitro. Association studies were performed using these polymorphisms and DNA isolated from 47 AAA patients, 57 intracranial aneurysm (IA) patients, and 174 controls, all from Finland. PAI-1 and MMP9 genotypes did not associate with aneurysms. The frequency of the 5A MMP3 allele was somewhat higher in the AAA than that in the control group (P = 0.0609 after Bonferroni correction), whereas the MMP3 allele frequencies in the IA group did not differ from those of the controls (P = 0.9667). These findings suggest that the transcriptionally more active 5A MMP3 allele might be a genetic risk factor for AAA among Finns. They are in agreement with previous studies demonstrating higher level of MMP3 expression in AAA than in control tissues.

Familial subarachnoid hemorrhage. Outcome study.

BACKGROUND AND PURPOSE: The aim of our study was to compare outcome and its determinants in familial subarachnoid hemorrhage and in sporadic subarachnoid hemorrhage in a large and well-documented patient population. METHODS: Patients with aneurysmal subarachnoid hemorrhage (SAH) treated at the Department of Neurosurgery, Kuopio University Hospital, from 1977 to 1995 were included. Patients with polycystic kidney disease were excluded. The Glasgow Outcome Scale (GOS) score at 12 months was studied. RESULTS: There were 120 patients (97 first-, 15 second-, and 8 third-degree family connections) in 96 different families with familial SAH and 1237 patients with sporadic SAH. Age, gender, and admission grade on the Hunt and Hess scale did not differ between these 2 groups. In both groups >80% of patients were in relatively good condition at admission. The outcome was good (GOS score of 1 to 2) in 87 patients (73%) with familial SAH and in 874 patients (71%) with sporadic SAH. Analysis of 20 variables, including presence of coexisting diseases, aneurysm site and size, amount of blood shown on CT scan, intraventricular bleeding, preoperative intracerebral hematoma and hydrocephalus, as well as postoperative bleeding and vasospasm, revealed no significant differences between study groups. The degree of family connection (first-, second-, and third-degree) did not have any statistically important effect on outcome in the familial group in the Finnish study population. In multivariate analysis the knowledge of familial SAH was not an independent prognostic factor. CONCLUSIONS: Admission status, postoperative course, and outcome were similar in the familial and sporadic SAH groups in this Finnish population, in contrast to previous results. Familial SAH may not be a significant risk factor for poor outcome.

Risk of harboring an unruptured intracranial aneurysm.

BACKGROUND AND PURPOSE: The purpose of the present study was to calculate the prevalence and relative risk of unruptured incidental intracranial aneurysms (IAs) among families with IA case(s) compared with the general population in one geographically defined area in East Finland and to identify the risk group that could benefit most from screening for IAs. We compared these results with our earlier study results of familial IA (FIA) cases, with two or more known IA cases in the same family. METHODS: The study groups were collected from the catchment area of the University Hospital of Kuopio in East Finland. The inclusion criteria were age 30 to 70 years and unruptured incidental IAs > or =3 mm. Patients with previous subarachnoid hemorrhage or in whom a ruptured IA was found to be the cause of death were excluded from all study groups. During routine forensic autopsies the circle of Willis was studied for IAs to estimate the number of IAs in the general population. In the families with one known IA case and in FIA families, MR angiography was used as a preliminary screening method for IAs, followed by intra-arterial angiography to verify suspected IAs. Study populations were age and sex adjusted for the statistical calculations. RESULTS: The relative risk for IAs among first-degree relatives in FIA families was 4.2 (95% confidence interval, 2.2 to 8.0) and among first-degree relatives in families with only one affected family member was 1.8 (95% confidence interval, 0.7 to 4.8) compared with the general population in East Finland. CONCLUSIONS: First-degree relatives in FIA families constitute a high-risk group for incidental IAs, and this group would benefit from screening studies for IAs. Screening for IAs in families with only one affected member or in the general population is not recommended.

Familial intracranial aneurysms.

BACKGROUND: We set out to determine the prevalence of incidental intracranial aneurysms in first-degree relatives aged 30 years or more of people with intracranial aneurysms, and to see if polycystic kidney disease contributes to the aggregation of familial intracranial aneurysms. METHODS: 91 families with two or more affected members had previously been identified from a 14 year series of 1150 intracranial aneurysm patients treated at the University Hospital of Kuopio, Finland. Magnetic resonance angiography was used as a preliminary screening method, followed by conventional four-vessel angiography to verify suspected aneurysms. Participants were also screened for polycystic kidneys by ultrasonography. FINDINGS: Incidental aneurysms were detected in 40 individuals: 38 of 438 individuals from 85 families without polycystic kidney disease or other diagnosed heritable disorders, and two of 22 individuals from six families known to have polycystic kidney disease. The crude and age-adjusted prevalence of incidental intracranial aneurysms among screened first-degree relatives was 8.7 (SE 1.3)% (95% CI 6.2-11.7) and 9.1 (1.4)% (6.2-11.7), respectively, for the familial group and the crude prevalence for the polycystic kidney group was 9.1 (6.1)% (1.1-29.2). INTERPRETATION: Our results demonstrate a high prevalence of incidental intracranial aneurysms among first-degree relatives aged 30 years or older of patients with the condition and indicate that the risk of having an aneurysm is about four times higher for a close relative than for someone from the general population. Also, polycystic kidney disease families are a small fraction of the familial intracranial aneurysm families.

Magnetic resonance angiographic screening for asymptomatic intracranial aneurysms: the problem of false negatives: technical case report.

To emphasize the limitations of magnetic resonance angiographic screening for intracranial aneurysms, we present the case of a patient with a false-negative screening result, unfortunately advancing to rupture of the aneurysm. An asymptomatic woman underwent magnetic resonance angiographic screening in an investigational setting. Three years later, she had an onset of sudden headache, after which her condition rapidly deteriorated. Severe subarachnoid hemorrhage and an intracerebral hematoma were diagnosed. Conventional angiography detected a small ruptured middle cerebral artery trifurcation aneurysm and two very small aneurysms. There are still limitations in the ability of magnetic resonance angiography to detect small or very small aneurysms. Even small-probability findings should always be confirmed or excluded by conventional angiography.

Special features of familial intracranial aneurysms: report of 215 familial aneurysms.

FAMILIAL INTRACRANIAL ANEURYSMS (FIAs) were compared with nonfamilial aneurysms (non-FIAs); the study group from east Finland included 167 family members from 85 families with FIAs. In every family, there has been two or more proven cases of subarachnoid hemorrhages among first-degree family members. Two-hundred and fifteen FIAs were found. The patients with FIAs were younger, and their aneurysms were smaller. Half of the FIAs were on the middle cerebral artery (n = 106 of 215), preferentially on the right side. Nearly one-third of the ruptured FIAs were smaller than 6 mm, and more than 80% of the aneurysms were under 14 mm in diameter. There were no significant differences between the frequency of aneurysms at mirror sites in FIA and non-FIA groups. Among siblings with FIAs, the frequency of pairs with age at onset within 10 years of each other was more than twice that expected from randomly selected pairs in the non-FIA group.

Intracranial aneurysms: MR angiographic screening in 400 asymptomatic individuals with increased familial risk.

PURPOSE: To evaluate the accuracy and limitations of magnetic resonance (MR) angiographic screening for incidental intracranial aneurysms (IAs) in healthy individuals with a family history of IA. MATERIALS AND METHODS: Four hundred asymptomatic individuals in 68 families with a history of aneurysmal subarachnoid hemorrhage underwent MR angiography. Six families also had a history of polycystic kidney disease. A multislab, three-dimensional, time-of-flight sequence was used. Conventional angiography was performed to confirm positive MR angiographic findings. RESULTS: IAs were detected with MR angiography in 37 individuals, 32 of whom underwent conventional angiography. Intraobserver consistency was excellent (kappa = 0.96), and interobserver reproducibility was good to excellent (kappa = 0.59-0.82). Both techniques showed similar results in the evaluation of size, localization, and orientation of aneurysms and visibility of the aneurysm neck. CONCLUSION: MR angiography is an accurate and feasible method of noninvasive screening for IAs in individuals at high risk. Conventional angiography is still necessary before operative treatment.