The “whisker sign” as an indicator of ochronosis in skeletal scintigraphy

A patient with alkaptonuria and ochronotic arthrosis was imaged twice with technetium-99m dicarboxypropane diphosphonate (^99mTc-DPD) — once during a bout of arthritic knee pain and once when symptom-free. There was a marked accumulation of radioactivity in the large joints. During the episode of arthritis the knee joints had a higher uptake than when the patient was without symptoms. The intervertebral discs showed a high uptake which extended laterally from the axial vertebral column; the finding gave an impression of whiskers, and this whisker sign may be characteristic of ochronosis.     

The Short and Long Forms of Type XVIII Collagen Show Clear Tissue Specificities in Their Expression and Location in Basement Membrane Zones in Humans

Two N-terminal ends of human type XVIII collagen chains have recently been identified. The two chains have different signal peptides and variant N-terminal noncollagenous NC1 domains of 493 (NC1-493) and 303 (NC1-303) amino acid residues, respectively, but share 301 residues of their NC1 domains as well as the collagenous and C-terminal noncollagenous portions of the molecule. Antibodies were produced against the NC1 region common to both human α1(XVIII) chain variants and against NC1 sequences specific to the long variant and were used in combination with in situ hybridization to localize this collagen in a number of human tissues. They were also used for Western blotting, which resulted in detection of overlapping high-molecular weight bands above the 200-kd standard in a kidney extract. Heparin lyase II and heparin lyase III digestions of kidney and placenta extracts indicated that at least in these tissues, type XVIII collagen contains heparin sulfate glycosaminoglycan side chains. Type XVIII collagen was found to be a ubiquitous basement membrane component, occurring prominently at vascular and epithelial basement membranes throughout the body. Comparison of the expression of the NC1-493 and NC1-303 variants revealed marked differences. The short variant was found in most conventional basement membranes, including blood vessels and the various epithelial structures, and around muscular structures. The long variant was expressed very strongly in liver, where it was virtually the only variant in the liver sinusoids, and it occurred only in minor amounts elsewhere. Thus, the 192 N-terminal residues specific to the long variant apparently confer some functional property needed above all in the liver sinusoids, but also at certain other locations.     

Prenatal sex determination by in situ hybridization on fetal nucleated cells in maternal whole venous blood

Our aim was to evaluate whether the sex of a fetus could be determined in maternal whole venous blood by in situ hybridization without enrichment of fetal cells. This procedure is virtually without risks to the fetus or the mother. Blood samples were obtained from 59 women at different stages of pregnancy. Twenty preparations were discarded because they were technically unfit for in situ hybridization. Of the remaining 39 pregnant women. 18 had a male fetus, one had male twins, and 20 had a female fetus. Y-positive cells were detected in 12 of the 19 pregnancies with male fetuses and in two of the 20 pregnancies with a female fetus. The frequencies of cells with Y-signals ranged from 1 in 100 000 to 1 in 639. Our results show that fetal cells in maternal blood cannot be reliably used for prenatal diagnosis without prior enrichment of fetal cells.     

Hsa-Mir-320c,Hsa-Mir-200c-3p,and Hsa-Mir-449c-5p as Potential Specific miRNA Biomarkers of COPD: A Pilot Study

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease commonly induced by cigarette smoke. The expression of miRNAs can be altered in patients with COPD and could be used as a biomarker. We aimed to identify a panel of miRNAs in bronchoalveolar lavage (BAL) to differentiate COPD patients from smokers and non-smokers with normal lung function. Accordingly, forty-five subjects classified as COPD, smokers, and non-smokers (n = 15 per group) underwent clinical, functional characterization and bronchoscopy with BAL. The mean age of the studied population was 61.61 ± 12.95 years, BMI 25.72 ± 3.82 Kg/m², FEV1/FVC 68.37 ± 12.00%, and FEV1 80.07 ± 23.63% predicted. According to microarray analysis, three miRNAs of the most upregulated were chosen: miR-320c, miR-200c-3p, and miR-449c-5p. These miRNAs were validated by qPCR and were shown to be differently expressed in COPD patients. ROC analysis showed that these three miRNAs together had an area under the curve of 0.89 in differentiating COPD from controls. Moreover, in silico analysis of candidate miRNAs by DIANA-miRPath showed potential involvement in the EGFR and Hippo pathways. These results suggest a specific 3-miRNA signature that could be potentially used as a biomarker to distinguish COPD patients from smokers and non-smoker subjects.     

Reoperations after first lumbar disc herniation surgery; a special interest on residives during a 5-year follow-up

Background  

The overall rate of operations after recurrent lumbar disc herniation has been shown to be 3–11%. However, little is known about the rate of residives. Thus the aim of this study was to explore the cumulative rates of re-operations and especially residive disc herniations at the same side and level as the primary disc herniation after first lumbar disc herniation surgery and the factors that influence the risk of re-operations over a five year follow-up study.     

Surgical treatment of Bertolotti's syndrome

Summary We surgically treated 16 patients with Bertolotti's syndrome (chronic, persistent low back pain and radiographically diagnosed transitional lumbar vertebra). Eight had posterolateral fusion and another eight resection of the transitional articulation. Thirteen patients had in addition to the chronic low back pain, suffered from repeated episodes or chronic sciatica. In six cases with resection treatment, local injections were administered at the transitional articulation before deciding for resection of the transitional joint; each patient reported transient relief of pain, while this preoperative test did not correlate with successful outcome of treatment. Six patients had to be treated with second operations. Ten of the 16 operatively treated patients showed improvement of the low back pain, and this result was similar in the group treated with fusion and in that treated with resection. Seven had no low back pain at follow-up, and the improvement according to the Oswestry pain scale was similar in the two groups, and statistically significant. Eleven patients still had persisting episodes of sciatica (versus 13 preoperatively). The average disability according to the Oswestry total disability scale was 30%, corresponding with moderate outcome, and both operatively treated groups did equally well. At follow-up the first disc above the fused segments was found to be degenerated in seven out of eight cases, and in the group treated with resection the first disc above the transitional vertebra was degenerated in five cases. As conservatively treated controls, we had 16 comparable, but not randomly chosen patients whose age and type and duration of pain prior to the first clinical examination, and the length of follow-up were similar to those in the operatively treated group. The operatively treated patients had slightly better Oswestry pain score (mean 1.9 versus 2.5; statistically significant), while in regard to the total Oswestry disability scale, the results did not differ. We suggest operative treatment only to very selected patients with Bertolotti's syndrome. Patients with no disc deneration and whose chronic pain is truly associated with the transitional joint may be treated with resection of the transverse process. Patients with similar pain and with degeneration of the disc below but not above the transitional vertebra may have alleviation of pain and disability after posterolateral fusion.     

The effect of subchronic administration of vigabatrin on learning and memory in nonepileptic rats

The present experiments investigated whether subchronic administration of vigabatrin, a GABA-mimetic drug, affects the performance of normal rats in the behavioural tasks assessing learning and memory. The effects of vigabatrin [50-200 mg/kg (IP)/day] administration on the acquisition and retention of water maze and passive avoidance task were studied. According to the results of three experiments, vigabatrin treatment did not markedly impair the acquisition or retention of water maze task. Furthermore, vigabatrin-treated rats were not inferior to saline-treated rats in reversal learning of water maze task. On the other hand, vigabatrin treatment slightly increased the speed of swimming in rats. The administration of vigabatrin did not affect the performance (training latency, number of training trials, testing latency) of rats in the passive avoidance task. According to these results, the effects of vigabatrin, a new antiepileptic drug, on the performance of nonepileptic rats were modest in behavioural tasks used to assess learning and memory.     

Remodeling of neuronal circuitries in human temporal lobe epilepsy: Increased expression of highly polysialylated neural cell adhesion molecule in the hippocampus and the entorhinal cortex

Neuronal loss and axonal sprouting are the most typical histopathological findings in the hippocampus of patients with drug-refractory temporal lobe epilepsy (TLE). It is under dispute, however, whether remodeling of neuronal circuits is a continuous process or whether it occurs only during epileptogenesis. Also, little is known about the plasticity outside of the hippocampus. We investigated the immunoreactivity of the highly polysialylated neural cell adhesion molecule (PSA-NCAM) in the surgically removed hippocampus and the entorhinal cortex of patients with drug-refractory TLE (n = 25) and autopsy controls (n = 7). Previous studies have shown that the expression of PSA-NCAM is associated with the induction of synaptic plasticity, neurite outgrowth, neuronal migration, and events requiring remodeling or repair of tissue. In patients with TLE, the optical density (OD) of punctate PSA-NCAM immunoreactivity was increased both in the inner and outer molecular layers of the dentate gyrus, compared with controls. The intensity of PSA-NCAM immunoreactivity in the inner molecular layer correlated with the duration of epilepsy, severity of hippocampal neuronal loss, density of mossy fiber sprouting, and astrogliosis. In TLE patients with only mild neuronal loss in the hippocampus, the density of infragranular immunopositive neurons was increased twofold compared with controls, whereas in TLE patients with severe neuronal loss, the infragranular PSA-NCAM–positive cells were not present. In the hilus, the somata and tortuous dendrites of some surviving neurons were intensely stained in TLE. PSA-NCAM immunoreactivity was also increased in CA1 and in layer II of the rostral entorhinal cortex, where immunopositive neurons were surrounded by PSA-NCAM-positive fibers and puncta. Our data provide evidence that synaptic reorganization is an active process in human drug-refractory TLE. Moreover, remodeling is not limited to the dentate gyrus, but also occurs in the CA1 subfield and the entorhinal cortex.     

Decreased muscle strength and mobility of the neck in patients with rheumatoid arthritis and atlantoaxial disorders

OBJECTIVE: To compare neck muscle strength and mobility of the cervical spine in rheumatoid arthritis (RA) patients with and without atlantoaxial (AA) disorders (anterior atlantoaxial subluxation [AAS], AA impaction). DESIGN: Clinical cross-sectional study. SETTING: Outpatient rheumatology and rehabilitation clinics in a Finnish hospital. PARTICIPANTS: Patients with RA (N=124; mean age +/- standard deviation, 62+/-12y [corrected]) on a waiting list for orthopedic surgery. Thirty (24%) patients presented with AA disorders (16 with anterior AAS, 8 with AA impaction, 6 with a combination of anterior AAS and AA impaction). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Neck function was measured by isometric neck strength and mobility tests, neck pain by a visual analog scale, erosion of the hands and feet by radiography, and the patients' function by the Health Assessment Questionnaire (HAQ). RESULTS: Maximal neck muscle strength against flexion, extension, and rotation was lower in patients with AA disorders compared with the other patients in both women (P=.012) and men (P=.017). Mobility was lowest in the AA impaction group in all measured directions (P<.001). Peripheral erosive disease was more frequent in the group with AA disorders. They also had longer disease duration and were more disabled (HAQ) than the other patients. CONCLUSIONS: Neck muscle strength is significantly decreased in patients with AA disorders. Mobility of the cervical spine is most limited in patients with AA impaction, but can be normal in cases with solitary anterior AAS.     

Does the outcome 2 months after lumbar disc surgery predict the outcome 12 months later?

Purpose : To assess the prognostic value of some preoperative and early post-operative indicators in the prediction of disability 14 months after lumbar disc surgery.

Methods : Of 173 patients, who had participated in baseline measurements, 145 (84%) attended the 14-month follow-up. Before surgery the duration and intensity of pain was assessed. Follow-up questionnaires were completed during check-ups and included items on pain (VAS), Oswestry and Million disability indices, depression (BDS) and work status.

Results : Two months after surgery average back pain was 67% lower and leg pain 70% lower than pre-operatively. The median Oswestry and Million disability indices were 14 and 15 at 2-months and remained low also at 14-months check-up. Further, the post-operative Oswestry and Million disability indices and BDS were highly associated with 14-month back and leg pain. Although the outcome of the patients was mostly good, 5% and 8% of them, respectively, reported severe pain at 2- and 14-month check-ups.

Conclusions : As recovery following lumbar disc surgery occurred to a great extent during the first 2 months, the early post-operative outcome appears to be quite a reliable indicator of the postoperative outcome in 1-year follow-up. The strong association between pain and the disability indices allows us to conclude that both the Million and Oswestry indices are clinically useful instruments in the evaluation of outcome in these cases.