Two year followup of anterior and vertical atlantoaxial subluxation in ankylosing spondylitis

OBJECTIVE: To describe the clinical and radiological 2-yr followup of 22 patients with anterior atlantoaxial subluxation (AAS) from a prospective cohort of patients with ankylosing spondylitis. METHODS: The 2-yr assessment included a structured questionnaire for rheumatologic and neurologic complaints and lateral cervical radiographs in maximal flexion view. Initial and 2-yr radiographs were assessed blind to patient data. The course of anterior AAS was classified as unchanged (< 1 mm), progression (> or = 1 mm) or regression (> or = 1 mm) at 2 yrs compared with baseline. Vertical AAS was classified using the Sakaguchi-Kauppi method. Magnification factor was corrected using the ratio of C3 width. RESULTS: Anterior AAS was detected in 22 patients at baseline examination. Two patients also had vertical AAS; 86% were male. Mean age was 33 +/- 9 yrs and mean disease duration was 12 +/- 7 yrs. At followup, one patient had died of acquired immunodeficiency syndrome, 3 could not be reached, and 2 had undergone surgical fusion due to severe myelopathy and now showed complete neurological recovery. Of the remaining 16 patients, 7 (32%) showed progression and 9 (41%) showed no change in the C1-odontoid distance. Vertical AAS developed in one patient. After the 2-yr assessment, 3 additional patients had surgical fusion because of notable progression of AAS, despite absence of neurological signs. CONCLUSION: Anterior AAS progressed in a number of these patients in the 2 yrs following its detection, and with or without neurological signs, surgical management was thought appropriate in a considerable number of them.     

Study of portal hypertension in children with special reference to sclerotherapy

Spinal cord injuries are rare in children, in face of their higher mobility comparing to adults. The high cervical and the thoracic segments of the spine are more frequently affected. In the last 10 years we had 90 cases of spinal injuries in our service being 12 with neurologic deficient (8 male and 4 female) and four of them without radiographic abnormality, even in the dynamics studies. The authors emphasise the possibility of occurrence of neurologic deficit in children after trauma, even without any radiographic abnormality.     

SAP97 is associated with the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit

Rapid glutamatergic synaptic transmission is mediated by ionotropic glutamate receptors and depends on their precise localization at postsynaptic membranes opposing the presynaptic neurotransmitter release sites. Postsynaptic localization of N-methyl-D-aspartate-type glutamate receptors may be mediated by the synapse-associated proteins (SAPs) SAP90, SAP102, and chapsyn-110. SAPs contain three PDZ domains that can interact with the C termini of proteins such as N-methyl-D-aspartate receptor subunits that carry a serine or threonine at the -2 position and a valine, isoleucine, or leucine at the very C terminus (position 0). We now show that SAP97, a SAP whose function at the synapse has been unclear, is associated with alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors. AMPA receptors are probably tetramers and are formed by two or more of the four AMPA receptor subunits GluR1-4. GluR1 possesses a C-terminal consensus sequence for interactions with PDZ domains of SAPs. SAP97 was present in AMPA receptor complexes immunoprecipitated from detergent extracts of rat brain. After treatment of rat brain membrane fractions with the cross-linker dithiobis(succinimidylpropionate) and solubilization with sodium dodecylsulfate, SAP97 was associated with GluR1 but not GluR2 or GluR3. In vitro experiments with recombinant proteins indicate that SAP97 specifically associates with the C terminus of GluR1 but not other AMPA receptor subunits. Our findings suggest that SAP97 may be involved in localizing AMPA receptors at postsynaptic sites through its interaction with the GluR1 subunit.     

Identification of 1,1'-bi(4-anilino)naphthalene-5,5'-disulfonic acid binding sequences in alpha-crystallin

The hydrophobic binding sites in alpha-crystallin were evaluated using fluorescent probes 1,1'-bi(4-anilino)naphthalenesulfonic acid (bis-ANS), 8-anilino-1-naphthalene sulfonate (ANS), and 1-azidonaphthalene 5-sulfonate (1,5-AZNS). The photolysis of bis-ANS-alpha-crystallin complex resulted in incorporation of the probe to both alphaA- and alphaB-subunits. Prior binding of denatured alcohol dehydrogenase to alpha-crystallin significantly decreased the photoincorporation of bis-ANS to alpha-crystallin. Localization of bis-ANS incorporated into alphaA-crystallin resulted in the identification of residues QSLFR and HFSPEDLTVK as the fluorophore binding regions. In alphaB-crystallin, sequences DRFSVNLNVK and VLGDVIEVHGK were found to be the bis-ANS binding regions. Of the bis-ANS binding sequences, HFSPEDLTVK of alphaA-crystallin and DRFSVNLNVK and VLGDVIEVHGK of alphaB-crystallin were earlier identified as part of the sequences involved in their interaction with target proteins during the molecular chaperone-like action. The hydrophobic probe, 1,5-AZNS, also interacted with both subunits of alpha-crystallin. Localization of 1,5-AZNS binding site in alphaB-crystallin lead to the identification of HFSPEEK sequence as the interacting site in this subunit of alpha-crystallin. Glycated alpha-crystallin displayed decreased ANS fluorescence and loss of chaperone-like function, suggesting the involvement of glycation site as well as ANS binding site in chaperone-like activity display.     

Measuring the quality of outpatient treatment for schizophrenia

OBJECTIVE: Usually it is not possible to study the initial systemic response in patients with acute pancreatitis in the first hours after onset of the disease. We used postendoscopic retrograde pancreatography (ERP) pancreatitis as a model to study cytokine and anticytokine release in the early phase of human acute pancreatitis. METHODS: Post-ERP pancreatitis was defined as a threefold increase in serum amylase and at least two of the following clinical symptoms: abdominal pain, nausea, vomiting or peritonism 24 h after ERP. Serum levels of pro-inflammatory cytokines interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor alpha (TNF), as well as endogenous antagonistic mediators of the systemic inflammatory response such as soluble tumour necrosis factor alpha receptors p55 (TNFR p55) and p75 (TNFR p75), and IL-1-receptor antagonist (IL-1-RA) and interleukin-2-receptor (IL-2R) as indicators of lymphocyte activation were measured before and 0, 1, 4, 12, 24 and 48 h after ERP. In nine patients with acute post-ERP pancreatitis, these parameters were monitored daily until C-reactive protein (CRP) was within normal ranges and were compared to patients without pancreatitis after ERP. RESULTS: IL-1beta was not detectable in five patients with and four patients without post-ERP pancreatitis. The values of the remaining patients in both groups were lower than 3.9 pg/ml. IL-8 and IL-1-RA serum concentrations peaked 12 h after ERP (132.9 and 3245.0 pg/ml respectively) compared to patients without post-ERP pancreatitis (25.8 and 389.9 pg/ml respectively). The IL-6 concentration increased to 81.6 pg/ml (8.0 pg/ml in control patients) 24 h after ERP, while the peak values for CRP were measured 72 h after ERP (164.0 versus 7.7 mg/l). IL-2R content was maximally elevated 144 h after ERP (688.8 versus 255.9 U/ml), while concentrations of TNF and its receptors showed no significant change over time. CONCLUSION: The initial response of the cytokine network to damage of the human pancreas leading to acute pancreatitis includes the release of IL-8 and the IL-1 antagonist IL-1-RA, while IL-1beta is not found in the systemic circulation. The TNF system does not seem to be involved as indicated by the lack of detectable changes in TNF and the soluble TNFR p55 and p75 serum concentrations. Lymphocyte activation as indicated by elevated IL-2R levels occurred days after the initial trauma. Even mild post-ERP pancreatitis leads to significant systemic release of cytokines and their biological counterparts.     

Doppler assessment of hemodynamic changes after hemodilution in retinal vein occlusion

Critical issues in diagnosis and treatment of pituitary disease are surveyed. The most relevant clinical aspects of hyperprolactinemia, acromegaly, Cushing's disease, secondary hyperthyroidism, syndrome of inappropriate ADH secretion, panhypopituitarism, growth hormone deficiency, gonadotropin deficiency, ACTH deficiency, TSH deficiency, and diabetes insipidus are discussed. Diagnostic and therapeutic issues in the approach to pituitary adenomas, craniopharyngiomas and pituitary apoplexy are analyzed.     

Effects of raloxifene on serum lipids and coagulation factors in healthy postmenopausal women

CONTEXT: Raloxifene is a selective estrogen receptor modulator that has estrogen-agonistic effects on bone and estrogen-antagonistic effects on breast and uterus. OBJECTIVE: To identify the effects of raloxifene on markers of cardiovascular risk in postmenopausal women, and to compare them with those induced by hormone replacement therapy (HRT). DESIGN: Double-blind, randomized, parallel trial. SETTING: Eight sites in the United States. PARTICIPANTS: 390 healthy postmenopausal women recruited by advertisement. INTERVENTION: Participants were randomized to receive 1 of 4 treatments: raloxifene, 60 mg/d; raloxifene, 120 mg/d; HRT (conjugated equine estrogen, 0.625 mg/d, and medroxyprogesterone acetate, 2.5 mg/d); or placebo. MAIN OUTCOME MEASURES: Change and percent change from baseline of lipid levels and coagulation parameters after 3 months and 6 months of treatment. RESULTS: At the last visit completed, compared with placebo, both dosages of raloxifene significantly lowered low-density lipoprotein cholesterol (LDL-C) by 12% (P < .001), similar to the 14% reduction with HRT (P < .001). Both dosages of raloxifene significantly lowered lipoprotein(a) by 7% to 8% (P < .001), less than the 19% decrease with HRT (P<.001). Raloxifene increased high-density lipoprotein-2 cholesterol (HDL2-C) by 15% to 17% (P < .05), less than the 33% increase with HRT (P < .001). Raloxifene did not significantly change high-density lipoprotein cholesterol (HDL-C), triglycerides, or plasminogen activator inhibitor-1 (PAI-1); whereas HRT increased HDL-C by 11% and triglycerides by 20%, and decreased PAI-1 by 29% (for all, P < .001). Raloxifene significantly lowered fibrinogen by 12% to 14% (P < .001), unlike HRT, which had no effect. Neither treatment changed fibrinopeptide A or prothrombin fragment 1 and 2. CONCLUSIONS: Raloxifene favorably alters biochemical markers of cardiovascular risk by decreasing LDL-C, fibrinogen, and lipoprotein(a), and by increasing HDL2-C without raising triglycerides. In contrast to HRT, raloxifene had no effect on HDL-C and PAI-1, and a lesser effect on HDL2-C and lipoprotein(a). Further clinical trials are necessary to determine whether these favorable biochemical effects are associated with protection against cardiovascular disease.     

Sclerotic lesions of the cervical spine in sarcoidosis

Sarcoidosis is a common multisystem disorder characterized by noncaseating epithelial granulomata, with osseous involvement typically seen in 5% of patients. While the lace-like or cystic pattern frequently seen in radiographs of the phalanges is well appreciated, sclerotic lesions of the spine are uncommon. We review a case of sarcoidosis of the cervical spine with sclerotic changes that mimicked blastic metastatic disease.