Retrospective patient outcome evaluation after semi-rigid stabilization without fusion for degenerative lumbar instability

Postero-lateral fusion by means of rod-and-screws/hooks constructs is still the gold standard in the treatment of lumbar degenerative spinal diseases. However, fusion remains fraught with a high risk of adjacent levels degeneration, sometimes leading to suboptimal clinical outcomes. Dynamic stabilization is supposed to compensate for disadvantages associated with rigid fusion. Preliminary results of spinal stabilization by means of dynamic devices show encouraging results. Therefore, the aim of the present study is to retrospectively evaluate the overall long term outcome and the condition of the adjacent discs to fused segments in an active population of 33 patients with back pain associated with lumbar instability, who underwent postero-lateral dynamic stabilization by means of a dynamic rod-and-screws construct, without fusion. The mean follow-up was 45 months. Clinical and radiological data, pain, function, return to work rate and patient satisfaction index were recorded to assess the overall patient outcome. The results show a very low rate of post-operative complications. No spontaneous fusion was noted in any patient. Pain, both lumbar and radicular, was totally relieved in most of the patients and the functional results were good or excellent in 76% of patients. Most of the patients resumed their previous activities; the return to previous work rate was 87.5%. Ninety-four percent of the patients were fully satisfied with the results. The preservation of both instrumented levels and the adjacent ones was observed in 90% of patients. Although the present series is rather limited in number, the results of the study are encouraging and in agreement with most findings in the literature. As the results are sustained at a mid and long term, the authors believe that the stabilization without fusion by means of semi-rigid/dynamic systems is an interesting alternative to classical fusion as long as the indications are strictly defined.     

Evaluation of myocardial function in patients with end-stage heart failure during support with the Jarvik 2000 left ventricular assist device.

In 2 patients with the Jarvik 2000 left ventricular assist device (LVAD), we assessed left ventricular systolic function through pressure-volume loops and E(max) at the beginning and end of the support period to potentially predict the possibility of pump removal without transplantation. Immediately before LVAD implantation and explantation, pressure and volume measurements were made with catheters and echocardiography, respectively, the E(max) being calculated from the slope of the pressure-volume loops, and the left ventricular ejection fraction (LVEF) being estimated by echocardiography. Transplantation was performed after 14 and 62 days, respectively, during which the LVEF increased by 75% (from 12% to 21%) in Patient 1 and remained unchanged (from 16% to 18%) in Patient 2, whereas the E(max) increased from 0.63 and 0.42 mm Hg/ml, respectively, to 1.31 and 1.07 mm Hg/ml, reflecting a 107% and 155% improvement. In these 2 cases, the E(max) was a more reliable indicator of intrinsic myocardial contractility than was the LVEF.     

Shared executive dysfunctions in unaffected relatives of patients with autism and obsessive-compulsive disorder.

BACKGROUND: Executive dysfunctions have been studied as a potential endophenotype associated with the genetic basis of autism. Given that recent findings from clinical and molecular genetic studies suggest that autism and obsessive-compulsive disorder (OCD) could share a common pattern of heritability, we assessed executive functions as a possible common cognitive endophenotype in unaffected family members of individuals with either autism or OCD. METHODS: Five tests assessing executive functions (Tower of London, verbal fluency, design fluency, trail making and association fluency) were proposed to 58 unaffected first-degree relatives (parents and siblings) of probands with autism and 64 unaffected first-degree relatives of OCD patients. Results were compared with those of 47 healthy controls matched for age, sex, and level of education. RESULTS: In the Tower of London test, both groups of unaffected relatives showed significantly lower scores and longer response times compared with controls. No differences were observed between autism and OCD relatives and healthy controls in the four other tasks (verbal fluency, design fluency, trail making test and association fluency). CONCLUSIONS: Our findings show the existence of executive dysfunction in the unaffected first-degree relatives of probands with OCD, similar to those observed in the relatives of patients with autism. These results support and extend previous cognitive studies on probands indicating executive dysfunctions in autism and OCD. Planning and working memory processes could thus represent a common cognitive endophenotype in autism and OCD that could help in the identification of genes conferring vulnerability to these disorders.     

Structural change in dopamine D2 receptor gene in a patient with neuroleptic malignant syndrome

Dysfunction of the dopaminergic system has been suggested as a pathogenic mechanism in neuroleptic malignant syndrome. Therefore, we examined the complete coding sequences of the dopamine D₂ receptor (DRD₂) gene for structural abnormalities in 12 patients with a history of NMS, including two cases of familial NMS. Mutational analysis was performed by denaturing gradient gel electrophoresis (DGGE), a highly sensitive technique for detecting sequence differences. We found in one patient with a history of NMS a nucleotide substitution at codon 310 (CCG→TCG) of exon 7 of the DRD₂ gene which predicts the replacement of proline to serine in the third cytoplasmic loop of the receptor, a part of the receptor that interacts with G-proteins. A larger series of patients with NMS needs to be investigated to establish whether this allele is associated with an increased susceptibility to NMS. © 1995 Wiley-Liss, Inc.     

Compartmentalized transgene expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) in mouse lung enhances allergic airways inflammation

To investigate the role of GM-CSF in asthmatic airways inflammation, we have targeted GM-CSF transgene to the airway cells in a mouse model of ovalbumin (OVA)-induced allergic airways inflammation, a model in which there is marked induction of endogenous IL-5 and IL-4 but not GM-CSF. Following intranasal delivery of a replication-deficient adenoviral gene transfer vector (Ad), transgene expression was found localized primarily to the respiratory epithelial cells. Intranasal delivery of 0.03 × 10⁹ plaque-forming units (PFU) of AdGM-CSF into naive BALB/c mice resulted in prolonged and compartmentalized release of GM-CSF transgene protein with a peak concentration of ≈ 80 pg/ml detected in bronchoalveolar lavage fluid (BALF) at day 7, but little in serum. These levels of local GM-CSF expression per se resulted in no eosinophilia and only a minimum of tissue inflammatory responses in the lung of naive mice, similar to those induced by the control vector. However, such GM-CSF expression in the airways of OVA-sensitized mice resulted in a much greater and sustained accumulation of various inflammatory cell types, most noticeably eosinophils, both in BALF and airway tissues for 15–21 days post-OVA aerosol challenge, at which times airways inflammation had largely resolved in control mice. While the levels of IL-5 and IL-4 in BALF and the rate of eosinophil apoptosis were found similar between different treatments, there was an increased number of proliferative leucocytes in the lung receiving GM-CSF gene transfer. Our results thus provide direct experimental evidence that GM-CSF can significantly contribute to the development of allergic airways inflammation through potentiating and prolonging inflammatory infiltration induced by cytokines such as IL-5 and IL-4.     

Tubular absorption of filtered cystatin-C in the rat kidney

As shown in previous studies, the two basic proteins aprotinin (Ap, 6.5 kDa) and cystatin (Cy, 13.3 kDa) can be used to estimate whole kidney glomerular filtration rate by measuring the renal cortical uptake relative to plasma concentration after i.v. injection. Local uptake of Ap can also be used to estimate local filtration rate, and the present experiments were undertaken to examine whether Cy would give a similar uptake pattern. Ap and Cy were labelled with 131I and 125I, respectively, and injected as an i.v. bolus. Frequent blood samples provided information on the filtered load. Five to 20 min after injection the kidney was clamped, frozen, and five tissue samples of 5-10 mg each were cut out from outer (OC), middle (MC) and inner cortex (IC) to be weighed and assessed for radioactivity. Five minute clearance ratios, Cy:Ap, were 1.36 +/- 0.04, 1.27 +/- 0.03 and 1.19 +/- 0.04 in OC, MC and IC, respectively. The higher Cy clearance was expected from a higher glomerular filtrate:plasma ratio of the less basic Cy (Donnan distribution). However, this does not explain the increase of Cy:Ap clearances going from IC to the OC. A surplus of extracellular uptake of Cy in superficial layers was excluded, leading to the following interpretation. In all cortical layers the proximal convoluted tubule, i.e. the protein uptake segment, is located more superficially than its parent glomerulus. A longer uptake segment for Cy than for Ap will therefore lead to a relative greater transfer of filtered Cy from IC to MC, and from MC to OC. Anatomical studies on single nephrons presented in another article lend strong support to this interpretation.