A Fast Scoring of Human Primary Respiratory Epithelia Grown at Air-Liquid Interface (ALI) to Assess Epithelial Morphology in Research and Personalized Medicine Settings.

BACKGROUND: In recent years, increasingly complex ALI protocols involving specialized, albeit laboratory-specific media have been established, while at the same time, many studies compile the data of only a few ALI donors in spite of site-, protocol- and donor-specific differentiation. METHODS: We describe a simple morphology scoring protocol using histology material derived from epithelia grown on ALI inserts in parallel to other, more complex readouts. RESULTS: Among more than 100 ALI inserts derived from different donors, significant differences in layer score (p = 0.001) and goblet cell score (p = 0.002) were observed when ALI epithelia derived from explanted lung material were compared to trachea-derived ALI cultures. Cortisol withdrawal for the final 2 days of ALI cultures influenced goblet cell density (p = 0.001). CONCLUSIONS: While the histology score provides less resolution than FACS- or OMICs- based single cell analyses, the use of a subportion of the ALI epithelia grown on inserts makes it feasible to combine morphology assessment and other readouts of the same insert. This allows us to control for basic ALI morphology in research and personalized medicine settings in order to assess and, if desired, control for the impact of ALI culture protocols, site- and donor-specific influences on outcome of studies of ALI-derived epithelia.

Long-term reintegration and quality of life in patients with subarachnoid hemorrhage and a good neurological outcome: findings after more than 20 years.

OBJECTIVE The goal of this study was to examine long-term quality of life (QOL) and reintegration in patients with good neurological recovery after aneurysmal subarachnoid hemorrhage (aSAH) and SAH of unknown cause (SAH NUD). METHODS A long-term follow-up was performed in an original cohort of 113 individuals who had suffered SAH (93 with aSAH and 20 with SAH NUD) between 1977 and 1984. Self-reporting assessments, performed > 20 years after the bleeding episode, included the Quality of Life Scale (QOLS), Psychological General Well-Being (PGWB) index, and Reintegration to Normal Living (RNL) index, along with information on sleep disturbances and work status. RESULTS Seventy-one survivors were identified. Questionnaires were returned by 67 individuals who had suffered SAH 20-28 years previously. The QOL was rated in the normal range for both the QOLS score (aSAH 90.3 vs SAH NUD 88.6) and the PGWB index (aSAH 105.9 vs SAH NUD 102.8). Ninety percent of patients had returned to their previous employment. Complete RNL was reported by 40% of patients with aSAH and by 46% of patients with SAH NUD; mild to moderate readjustment difficulties by 55% and 38%, respectively; and severe difficulties by 5% of patients with aSAH and 15% of patients with SAH NUD. Self-rated aspects of cognition, mood, and energy resources in addition resulted in a substantial drop in overall reintegration. Sleep disturbances were reported by 26%. CONCLUSIONS More than half of patients with SAH who had early good neurological recovery experienced reintegration difficulties after > 20 years. However, the general QOL was not adversely affected by this impairment. Inability to return to work after SAH was associated with lower QOLS scores. Sleep disturbances were associated with lower PGWB scores.

Transforaminal steroid injections for the treatment of cervical radiculopathy: a prospective and randomised study.

Steroid injections are often employed as an alternative treatment for radicular pain in patients with degenerative spinal disorders. Prospective randomised studies of the lumbar spine reveal contradictory results and non-randomised and most often retrospective studies of the cervical spine indicate pain reduction from steroid injections. No prospective randomised study on transforaminal steroid injections for the treatment of radicular pain in the cervical spine focusing on short-term results has been performed. Forty consecutive patients were employed for the study. The inclusion criteria were one-sided cervical radiculopathy with radicular distribution of arm pain distal to the elbow and corresponding significant degenerative pathology of the cervical spine at one or two levels on the same side as the radicular pain and visualised by MRI. A transforaminal technique was used for all injections. A positive response to a diagnostic selective nerve root block at one or two nerve roots was mandatory for all patients. The patients were randomised for treatment with steroids/local anaesthetics or saline/local anaesthetic. Only the neuroradiologist performing the blocks was aware of the content of the injection; all other persons involved in the study were blinded. Follow up was made 3 weeks after the randomised treatment by a clinical investigation and with a questionnaire focusing on the subjective effects from the injections. At follow up, there were no differences in treatment results in the two patient groups. Statistical analysis of the results confirmed the lack of difference in treatment effect. Further studies have to be performed before excluding steroids in such treatment and for evaluating the influence of local anaesthetics on radiculopathy in transforaminal injections.

Selective diagnostic nerve root block for the evaluation of radicular pain in the multilevel degenerated cervical spine.

In patients with radiculopathy due to degenerative disease in the cervical spine, surgical outcome is still presenting with moderate results. The preoperative investigations consist of clinical investigation, careful history and most often magnetic resonance imaging (MRI) of the cervical spine. When MRI shows multilevel degeneration, different strategies are used for indicating which nerve root/roots are affected. Some authors use selective diagnostic nerve root blocks (SNRB) for segregating pain mediating nerve roots from non-pain mediators in such patients. The aim of the present study is to assess the ability of transforaminal SNRB to correlate clinical symptoms with MRI findings in patients with cervical radiculopathy and a two-level MRI degeneration, on the same side as the radicular pain. Thirty consecutive patients with cervical radiculopathy and two levels MRI pathology on the same side as the radicular pain were studied with SNRBs at both levels. All patients underwent clinical investigation and neck and arm pain assessment with visual analogue scales (VAS) before and after the blocks. The results from the SNRBs were compared to the clinical findings from neurological investigation as well as the MRI pathology and treatment results. Correlation between SNRB results and the level with most severe degree of MRI degeneration were 60% and correlation between SNRB results and levels decided by neurological deficits/dermatome radicular pain distribution were 28%. Twenty-two of the 30 patients underwent treatment guided by the SNRB results and 18 reported good/excellent outcome results. We conclude that the degree of MRI pathology, neurological investigation and the pain distribution in the arm are not reliable parameters enough when deciding the affected nerve root/roots in patients with cervical radiculopathy and a two-level degenerative disease in the cervical spine. SNRB might be a helpful tool together with clinical findings/history and MRI of the cervical spine when performing preoperative investigations in patients with two or more level of degeneration presenting with radicular pain that can be attributed to the degenerative findings.

Impact of coil embolization on overall management and outcome of patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: We report on the consequences of introducing coil embolization for the total management of and outcome in patients with subarachnoid hemorrhage (SAH). METHODS: In southern Sweden, a prospective analysis of all patients with SAH of verified aneurysmal origin was conducted during the 3 years when coiling was gradually being introduced. The incidence of acute or chronic hydrocephalus, vasospasm, delayed ischemic deterioration, and outcome at 3 to 6 months after bleeding was analyzed. RESULTS: Coiling of aneurysms was used progressively more compared with clipping during the study period. The number of patients subjected to coiling was 26 (36%) of 73 patients during calendar year 1997, 43 (53%) of 81 patients in 1999, and 55 (74%) of 74 patients in 2001 (P < 0.0001). Gradually, more elderly patients were admitted during the study period. Virtually all aneurysms located in the posterior circulation were treated by coil embolization, even at the start of the study, whereas aneurysms at all other locations were progressively more likely to be treated similarly. The incidence of hydrocephalus in the acute (average for all 3 yr, 39%) or chronic (16%) phase, vasospasm as measured by Doppler sonography (33%), and delayed ischemic deterioration (29%), as well as outcome at 3 to 6 months (61% good recovery, 13% deceased), did not change significantly during the study. The main cause of unfavorable outcome was the severity of the SAH. CONCLUSION: The increasing use of coil embolization for ruptured aneurysms in the anterior circulation did not have any significant impact on the overall incidence of SAH-related complications or outcome. The main determinant for outcome after SAH is still the severity of the SAH.

Transcranial Doppler sonography pulsatility index (PI) reflects intracranial pressure (ICP).

BACKGROUND: In patients with intracranial pathology, especially when comatose, it is desirable to have knowledge of the intracranial pressure (ICP). To investigate the relationship between ICP and transcranial Doppler (TCD) derived pulsatility index (PI) in neurosurgical patients, a prospective study was performed on patients admitted to our neurointensive care unit. METHODS: Daily TCD mean flow velocity (mFV) measurements were made. TCD measurements were routinely performed bilaterally on the middle cerebral artery (MCA). PI (peak systolic-end diastolic velocities/mean flow velocity) was calculated. RESULTS: Eighty-one patients with various intracranial disorders who had an intraventricular catheter for registration of the ICP were investigated: 46 (57%) patients had subarachnoid hemorrhage, 21 (26%) patients had closed head injury, and 14 (18%) patients had other neurosurgical disorders. A total of 658 TCD measurements were made. ICP registrations were made parallel with all TCD measurements. A significant correlation (p < 0.0001) was found between the ICP and the PI with a correlation coefficient of 0.938: ICP = 10.93 x PI - 1.28. In the ICP interval between 5 to 40 mm Hg the correlation between ICP and PI enabled an estimation of ICP from the PI values with an SD of 2.5. The correlation between the cerebral perfusion pressure (CPP) and PI was significant (p < 0.0001) with a correlation coefficient of -0.493. When separating the measurements in severely elevated (>120 cm/s) and subnormal (<50 cm/s) TCD mFV values, the correlation coefficient between ICP and PI was 0.828 (p < 0.002) and 0.942 (p < 0.638), respectively. CONCLUSIONS: Independent of the type of intracranial pathology, a strong correlation between PI and ICP was demonstrated. Therefore, PI may be of guiding value in the invasive ICP placement decision in the neurointensive care patient.

Prediction of death in patients with primary intracerebral hemorrhage: a prospective study of a defined population.

OBJECT: Predictors of early (30-day) and long-term (1-year) mortality rates after primary intracerebral hemorrhage (ICH) were studied in a large population in southern Sweden. METHODS: All cases of primary ICH, verified using computerized tomography (CT) scanning or autopsy study, were prospectively registered at the 12 hospitals covering a defined population of 1.14 million during the calendar year 1996. Mortality was analyzed in relation to CT findings (hematoma location and volume and ventricular extension) and clinical parameters (patient age and sex, level of consciousness on admission, and history of preictal risk factors) by using univariate and multivariate statistical methods. Three hundred forty-one cases of primary ICH were detected. The overall mortality rate was 36% at the 30-day and 47% at the 1-year follow up. Multivariate analysis revealed that initial level of consciousness, hematoma volume, and a history of heart disease were independent predictors of death at 30 days postictus. One year after bleeding, independent predictors of mortality were the initial level of consciousness, patient age, and hematoma location. CONCLUSIONS: Primary ICH remains a stroke subtype associated with a high mortality rate and for which the level of consciousness on admission is the strongest predictor of fatal outcome both at 30 days and during the 1st year after bleeding. A preictal history of heart disease increased the 30-day mortality rate.

Intraoperative complications in aneurysm surgery: a prospective national study.

OBJECT: With increasing use of endovascular procedures, the number of aneurysms treated surgically will decline. In this study the authors review complications related to the surgical treatment of aneurysms and address the issue of maintaining quality standards on a national level. METHODS: A prospective, nonselected amalgamation of every aneurysm case treated in five of six neurosurgical centers in Sweden during 1 calendar year was undertaken (422 patients; 7.4 persons/100,000 population/year). The treatment protocols at these institutions were very similar. Outcome was assessed using clinical end points. In this series, 84.1% of the patients underwent surgery, and intraoperative complications occurred in 30% of these procedures. Poor outcome from technical complications was seen in 7.9% of the surgically treated patients. Intraoperative aneurysm rupture accounted for 60% and branch sacrifice for 12% of all technical difficulties. Although these complications were significantly related to aneurysm base geometry and the competence of the surgeon, problems still occurred apparently at random and also in the best of hands (17%). The temporary mean occlusion time in the patients who suffered intraoperative aneurysm rupture was twice as long as the temporary arrest of blood flow performed to aid dissection. CONCLUSIONS: The results obtained in this series closely reflect the overall management results of this disease and support the conclusion that surgical complications causing a poor outcome can be estimated on a large population-based scale. Intraoperative aneurysm rupture was the most common and most devastating technical complication that occurred. Support was found for a more liberal use of temporary clips early during dissection, regardless of the experience of the surgeon. Temporary regional interruption of arterial blood flow should be a routine method for aneurysm surgery on an everyday basis. A random occurrence of difficult intraoperative problems was clearly shown, and this factor of unpredictability, which is present in any preoperative assessment of risk, strengthens the case for recommending neuroprotection as a routine adjunct to virtually every aneurysm operation, regardless of the surgeon's experience.

Aneurismas: una experiencia escandinava; manejo de la ruptura de aneurismas intracraneanos; un analisis / Aneurisms: scandinavian experience; management of the intracranial aneurisms rupture; analysis

Se revisa la desalentadora historia asociada al manejo de la hemorragia subaracnoidea de los aneurismas (HSA), junto a los posibles perfeccionamientos atribuibles al progreso de la última década . Entre los nuevos avances se encuentra la introducción de técnicas micro-quirúrgicas que permiten la cirugía electiva en la etapa aguda, previniendo de este modo la repetición de las hemorragias. La operación temprana también ofrece la posibilidad de un tratamiento farmacológico anti-isquémico más agresivo. No obstante, los mejores resultados de la cirugía electiva aguda y el hecho de que el deterioro isquémico retardado (vasoespasmo cerebral sintomático) pueden estar practicamente eliminados en la actualidad, el resultado global es pesimista. A pesar de los recientes adelantos no se espera que más de una de tres personas que sufran la ruptura de un aneurisma intracraneano puedan tener una buena recuperación funcional y neurológica. La esperanza de nuevos progresos puede depender de desarrollo de técnicas que identifiquen los aneurisamas intracraneanos antes de su rompimiento y del aumento de conocimientos sobre la etiología de dichas lesiones de la pared arterial