Correction of pelvic obliquity in neuromuscular spinal deformities using the “T construct”: results and complications in a prospective series of 60 patients

Background

We present the results of a prospective series of 60 patients treated for neuromuscular spinal deformities with an original spinopelvic construct using two sacral screws and two iliac screws. Clinical and radiological results obtained with this new surgical technique were studied and discussed according to the epidemiological data and relevant literature.

Methods

From January 2008 to June 2010, the clinical data of every patient who underwent spinopelvic fixation for treatment of a neuromuscular spinal deformity were recorded prospectively.

Results

Sixty patients were operated on during the study period. Spinal correction and fusion was performed by posterior approach. In six patients with a residual spinopelvic imbalance more than 15° on lateral preoperative bending films, an anterior release of the thoracolumbar junction was performed on the same day, before posterior correction. Preoperative pelvic obliquity (PO) ranged from 4° to 44° (mean 21.6°). Postoperative pelvic obliquity ranged from 0° to 14 (mean 4.6°). No significant loss of correction was noted at the last follow-up. One patient died 3 months after the initial procedure due to respiratory compromise. 11 patients had early postoperative infections of the posterior approach.

Conclusions

Despite a high rate of infectious complications, optimal correction of pelvic obliquity requires extension of spinal instrumentation to the pelvis. Spinopelvic fixation remains a difficult challenge in neurological patients with hypotrophy. We think that pelvic fixation with the “T construct” did provide effective and improved spinal stabilization in these patients, while reducing the need for a postoperative cast or brace. As a result, patients had a favourable postoperative course with early mobilization and return to a comfortable sitting position.     

血液病及实体瘤T-淋巴细胞亚群的表达

为了研究各种血液病、良性和恶性肿瘤T-淋巴细胞亚群变化关系,及其对诊断、治疗及预后的价值,采用流式细胞术、Cellquest软件及Modfie软件,对1 112例各种血液病、良性和恶性肿瘤的患者进行测定和比较,求出相关性.结果发现,慢性白血病CD3,CD4,CD8和CD4/CD8各项指标极度减低;急性白血病、MDS各项检测指标均较正常人及其它血液病患者明显下降,相互之间有显著差异(P＜0.01);溶血性贫血患者的各项检测指标较正常人及其它各组患者明显增高,尤其CD3,CD4及CD4/CD8比值增高更明显(P＜0.05);特发性血小板减少性紫癜患者CD3,CD4及CD4/CD8比值较正常人明显减低,但与再生障碍性贫血和其它疾病接近,而CD8明显高于正常人及其它血液病、肿瘤患者相互之间有显著差异(P＜0.01);缺铁性贫血、慢性病性贫血、良性肿瘤和其它血液病患者CD3,CD4和CD8虽然均较正常人及溶血性贫血患者有不同程度的减低,但较急性和慢性白血病、恶性肿瘤、粒细胞减少症、MDS患者有不同程度增高,相互之间无显著性差异.值得注意的是,上述各种检测指标异常与治疗前后,以及疾病进展、缓解、预后呈正相关.结论血液病和恶性肿瘤T-细胞亚群各项检测指标对血液病和良、恶性肿瘤诊断及鉴别诊断,以及正确指导治疗及评价预后有重要实用价值,特别对恶性血液病、恶性肿瘤转归有更重要的意义,是目前测定体内免疫活性的最适指标.     

Identification of an erm(T) gene in strains of inducibly clindamycin-resistant group B Streptococcus

Five inducibly clindamycin (CLI)-resistant group B Streptococcus (GBS) isolates, all negative for erm(A) and erm(B) genes, were found to contain erm(T), a gene previously reported in erythromycin-resistant animal isolates of Lactobacillus spp. and human isolates of Streptococcus bovis. One additional GBS isolate, constitutively resistant to CLI, was also positive for the erm(T) gene in addition to erm(B). To our knowledge, this is the 1st report of erm(T) in GBS, the 2nd bacterial species from humans in which the erm(T) gene has been identified, and the 3rd erm gene to be found in GBS.     

SH2D1A regulates T-dependent humoral autoimmunity

The signaling lymphocytic activation molecule (SLAM)/CD150 family includes a family of chromosome 1-encoded cell surface molecules with costimulatory functions mediated in part by the adaptor protein SH2D1A (SLAM-associated protein, SAP). Deficiency in SH2D1A protects mice from an experimental model of lupus, including the development of hypergammaglobulinemia, autoantibodies including anti-double stranded DNA, and renal disease. This protection did not reflect grossly defective T or B cell function per se because SH2D1A-deficient mice were susceptible to experimental autoimmune encephalomyelitis, a T cell-dependent disease, and they were capable of mounting normal T-independent antigen-specific immunoglobulin responses. Instead, T-dependent antibody responses were impaired in SH2D1A-deficient mice, reflecting defective germinal center formation. These findings demonstrate a specific role for the SLAM-SH2D1A system in the regulation of T-dependent humoral immune responses, implicating members of the CD150-SH2D1A family as targets in the pathogenesis and therapy of antibody-mediated autoimmune and allergic diseases.     

Early replacement therapy in a first Japanese case with autosomal recessive guanosine triphosphate cyclohydrolase I deficiency with a novel point mutation

Autosomal recessive guanosine triphosphate cyclohydrolase I (GTPCH) deficiency is an inborn error of tetrahydrobiopterin (BH4) synthesis from GTP. GTPCH deficiency causes severe reduction of BH4, resulting in hyperphenylalaninemia (HPA) and decreased dopamine and serotonin synthesis. Without treatment, a patient with GTPCH deficiency develops complex neurological dysfunctions, including dystonia and developmental delays. The first Japanese patient with GTPCH deficiency was discovered by HPA during asymptomatic newborn screening. The phenylalanine level at the age of 5 days was 1273 μmol/L (cutoff value, 180.0 μmol/L). The high serum phenylalanine level was decreased to normal after adequate BH4 oral supplementation. Serum and urinary pteridine examination revealed very low levels of neopterin and biopterin. Sequence analysis of GCH1 revealed compound heterozygous point mutations, including a novel point mutation (p.R235W). Replacement therapy with BH4 and L-dopa/carbidopa were started at the age of 1 month, and 5-hydroxytryptophan (5-HTP) was started at the age of 5 months. At 10 months of age, the patient showed slight dystonia but no obvious developmental delay. Cerebrospinal fluid should be examined to determine the appropriate dosage of supplement drugs. In conclusion, it is important to control the serum phenylalanine level and perform early replacement of neurotransmitters to prevent neurological dysfunction.     

Different patterns of cerebellar abnormality and hypomyelination between POLR3A and POLR3B mutations

Background

Mutations of POLR3A and POLR3B have been reported to cause several allelic hypomyelinating disorders, including hypomyelination with hypogonadotropic hypogonadism and hypodontia (4H syndrome). Patients and methods: To clarify the difference in MRI between the two genotypes, we reviewed MRI in three patients with POLR3B mutations, and three with POLR3A mutations. Results: Though small cerebellar hemispheres and vermis are common MRI findings with both types of mutations, MRI in patients with POLR3B mutations revealed smaller cerebellar structures, especially vermis, than those in POLR3A mutations. MRI also showed milder hypomyelination in patients with POLR3B mutations than those with POLR3A mutations, which might explain milder clinical manifestations. Conclusions: MRI findings are distinct between patients with POLR3A and 3B mutations, and can provide important clues for the diagnosis, as these patients sometimes have no clinical symptoms suggesting 4H syndrome.     

Neurodevelopmental and behavioral effects of nonylphenol exposure during gestational and breastfeeding period on F1 rats

Nonylphenols (NP) are endocrine-disruptors known to be widely present in our environment. This study evaluated the effects of 4-n-NP on neurobehavioral development and memory capacity after perinatal exposure on the offspring rats. Dams were gavaged with 4-n-NP (0, 50 and 200 mg/kg/day) from gestational day 5 to postnatal day (PND) 21. Dams exposed to the higher dose lost weight during gestation and had a longer gestational duration. Juvenile female pups of the 200 mg 4-n-NP/kg/day group were lighter. Their thyroid somatic index (TSI) was also affected. For male pups, a decrease of TSI at weaning for the 200 mg 4-n-NP/kg/day group and an increase of GSI for the 50 mg 4-n-NP/kg/day group were observed. Physical maturation (incisives and eyes) were likewise affected. In open field (OF) tests, females were more active than males. In the first OF (PND 36), a treatment effect was observed only for males, particularly for the high dose group, which became as active as females. The second OF (PND 71) showed few differences between groups (treated vs control), the gender difference whatever the dose was not abolished. In the Morris Water Maze test, the study of the first 30 s showed that females (200 mg/kg/day) were mainly affected. Their performances were improved by 4-n-NP. These effects were particularly important for the first short-term memory test and observed to a lesser extent in the second evaluation of the long-term memory (PND 69). These data showed that perinatal 4-n-NP exposure induced behavioral and neuro-developmental impairments from 50 mg/kg/day.     

TRPM4 channels couple purinergic receptor mechanoactivation and myogenic tone development in cerebral parenchymal arterioles

Cerebral parenchymal arterioles (PAs) have a critical role in assuring appropriate blood flow and perfusion pressure within the brain. They are unique in contrast to upstream pial arteries, as defined by their critical roles in neurovascular coupling, distinct sensitivities to chemical stimulants, and enhanced myogenic tone development. The objective of the present study was to reveal some of the unique mechanisms of myogenic tone regulation in the cerebral microcirculation. Here, we report that in vivo suppression of TRPM4 (transient receptor potential) channel expression, or inhibition of TRPM4 channels with 9-phenanthrol substantially reduced myogenic tone of isolated PAs, supporting a key role of TRPM4 channels in PA myogenic tone development. Further, downregulation of TRPM4 channels inhibited vasoconstriction induced by the specific P2Y4 and P2Y6 receptor ligands (UTPγS and UDP) by 37% and 42%, respectively. In addition, 9-phenanthrol substantially attenuated purinergic ligand-induced membrane depolarization and constriction of PAs, and inhibited ligand-evoked TRPM4 channel activation in isolated PA myocytes. In concert with our previous work showing the essential contributions of P2Y4 and P2Y6 receptors to myogenic regulation of PAs, the current results point to TRPM4 channels as an important link between mechanosensitive P2Y receptor activation and myogenic constriction of cerebral PAs.