Elevation of cerebrospinal fluid soluble CD27 levels in patients with meningeal localization of lymphoid malignancies [published erratum appears in Blood 1996 Oct 1;88(7):2818]

Diagnosis of meningeal localization of lymphoid malignancies by means of cytologic examination of the cerebrospinal fluid (CSF) can be difficult. Thus far no reliable CSF tumor markers have been identified. CD27 is a transmembrane disulfide-linked 55-kD homodimer present on most peripheral blood T cells and on a subset of B cells. CD27 is also expressed on human malignant B cells and high levels of soluble CD27 can be present in the serum of patients with B-cell malignancies. The aim of this study is to determine prospectively the diagnostic value of CSF sCD27 as a tumor marker in patients with meningeal localization of lymphoid malignancies. CSF sCD27 levels were determined by sandwich enzyme-linked immunosorbent assay. The optimal cut-off value using receiver operator characteristics curves was found to be 10 U/mL. sCD27 levels were normal in all 50 control patients (lumbar disc protrusion) and in 39 of 40 samples obtained from patients with either solid tumors or acute myeloid leukemia. Of 104 CSF samples from 70 children with acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) undergoing routine central nervous system (CNS) staging, sCD27 was false positive and false negative in only one sample each. In 70 samples from 45 patients suspected of meningeal localization of ALL or NHL, the sCD27 test had an excellent sensitivity (100%) and specificity (82%). In 7 patients with positive CSF studied longitudinally, sCD27 levels correlated very well with remission and relapse. sCD27 levels were not nonspecifically increased by the administration of cytostatic drugs. Finally, sCD27 was also elevated in the 4 patients studied with primary central nervous system lymphoma (PCNSL). CSF sCD27 is a promising tumor marker in patients with either meningeal localization of lymphoid malignancies or PCNSL, and can be useful in the differential diagnosis of CNS involvement by either lymphoid malignancies or solid tumors.     

Optic disc haemorrhages and vascular abnormalities in a glaucoma population

Purpose: To retrospectively examine the optic disc photographs of a glaucoma population for optic disc haemorrhages, vascular occlusions and vascular abnormalities. Methods: The optic disc photographs of 906 eyes of glaucoma and suspect glaucoma patients were examined. Optic disc photographs were taken annually, where possible, with the follow-up period varying between 1 and 14 years duration (mean, 2.89). Glaucoma patients are regularly reviewed every 4–6 months and glaucoma suspects every 1–2 years, depending on the ophthalmologist. Low-tension glaucoma patients were reviewed more frequently (mean, every 2.6 months). The results of the findings were compared to a control group of 39 subjects with a mean follow-up period of 7 years, using Fisher's exact test. Results: It was found that during the period under review, 7.4% (n= 67) of eyes had optic disc haemorrhages. The highest frequency of optic disc haemorrhages (37.5%) was found in the low tension glaucoma group (P= 0.0001) followed by 11.4% of primary open-angle glaucoma eyes (P= 0.03). In the normal group there were three eyes with optic disc haemorrhages and one with a disc collateral, which constitutes 5.1% vascular changes in this sub-group. Of the study eyes 2.8% had central retinal vein occlusions, 1.3% branch vein occlusion, 1.2% disc vessel abnormalities (loops) and 1.1% disc collaterals. Discrete nerve fibre layer haemorrhages and microaneurysms were found in 0.8% and 1.8% of eyes, respectively. Conclusions: A total of 16.8% of the eyes observed in this study had either disc haemorrhages or vascular changes. The underlying trend of vascular and haemorrhagic changes in glaucoma are demonstrated in this sample, which is in general agreement with previous studies. The high percentage of optic disc haemorrhages in low tension glaucoma is highlighted. The presence of microaneurysms and nerve fibre layer haemorrhages is interesting but of unknown significance.     

Association of pupillary parasympathetic hyperreflexia and systemic inflammation in patients with systemic lupus erythematosus

In chronic inflammatory diseases, cytokines stimulate the hypothalamus pituitary adrenal axis and the hypothalamus autonomic nervous system (HANS) axis. The present study was performed to find autonomic nervous function parameters in patients with systemic lupus erythematosus (SLE) which are suitable to demonstrate the activation of the HANS axis during systemic inflammation. Thirty-four patients with SLE (age 35.3 +/- 1.9 yr) were investigated by seven standardized autonomic nervous function tests. The SLEDAI and laboratory parameters of systemic inflammation were assessed by standard techniques. Pupillary latency time hyperreflexia was found in 29.4%, whereas maximal pupillary area was hyperresponsive in only 2.9%. A total of 12% had overall cardiovascular autonomic nervous hyperreflexia. Patients with latency time hyperreflexia had more severe systemic inflammation [erythrocyte sedimentation rate (ESR): P < 0.001; C-reactive protein (CRP): P = 0.0094; fibrinogen: P < 0.001; albumin: P = 0.003; antinuclear antibodies: P = 0.020]. The longitudinal study of 13 patients during 4 yr demonstrated a parallel increase and decrease in latency time percentile and ESR. SLE patients with increased systemic inflammation had an activated HANS axis which can be measured by a parasympathetic pupillary reflex test.      

Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency

Homocysteine can be methylated to form methionine by the cobalamin- (Cbl) and folate-dependent enzyme, methionine synthase; serum levels of total homocysteine are elevated in greater than 95% of patients with either Cbl or folate deficiency. Homocysteine can also condense with serine to form cystathionine in a pyridoxal phosphate-dependent reaction catalyzed by cystathionine beta-synthase. Cystathionine is subsequently cleaved to cysteine and alpha-ketobutyrate by the pyridoxal phosphate-dependent enzyme gamma-cystathionase. To assess levels of cystathionine in Cbl and folate deficiency, we developed a new capillary gas chromatographic-mass spectrometric assay and measured cystathionine in the serum of normal subjects and patients with clinically confirmed deficiencies of these vitamins. The normal range for serum cystathionine was 65 to 301 nmol/L (median = 126 nmol/L) for 50 normal blood donors. In 30 patients with clinically confirmed Cbl deficiency, values for cystathionine ranged from 208 nmol/L to 2,920 nmol/L (median = 816 nmol/L) and 26 (87%) had levels above the normal range. In 20 patients with clinically confirmed folate deficiency, cystathionine concentrations ranged from 138 nmol/L to 4,150 nmol/L (median = 1,560 nmol/L) and 19 (95%) had values above the normal range. Five homozygotes for cystathionine beta-synthase deficiency had high values for serum-total homocysteine and low or low-normal values for serum cystathionine that ranged from 30 nmol/L to 114 nmol/L even though they were on treatment with pyridoxine and had partially responded. One patient with a defect in the synthesis of 5-CH3- tetrahydrofolate and five patients with defects in the synthesis of CH3- Cbl had high values for serum-total homocysteine and high values for cystathionine that ranged from 311 nmol/L to 1,500 nmol/L even though they were on treatment with folic acid and Cbl, respectively, and had partially responded. We conclude that levels of cystathionine are evaluated in the serum of most patients with Cbl and folate deficiency and that they are useful in the differential diagnosis of an elevated serum-total homocysteine level.     

Comparison between published clinical success of direct resin composite restorations in vital posterior teeth in 1995–2005 and 2006–2016 periods

Composites are increasing in popularity as restorative materials. This growing role indicates the necessity of studies on their clinical outcome. In this study, clinical studies published on the performance of posterior composite restorations were included except those of less than a 24‐month assessment period. Results of non‐vital, anterior or primary teeth and cervical single‐surface restorations were also excluded. Records about composite type, number of final recall restorations, failure/survival rate, assessment period and failure reasons were analysed for each decade. Overall survival/failure rates for studies in 1995–2005 were 89.41%/10.59% and for 2006–2016 were 86.87%/13.13%, respectively. In 1995–2005, the reasons for failure were secondary caries (29.47%) and composite fracture (28.84%) with low tooth fracture (3.45%) compared with reasons of failure in 2006–2016, which were secondary caries (25.68%), composite fracture (39.07%), and tooth fracture (23.76%). An increase in incidence of composite fracture, tooth fracture and need for endodontic treatment as failure reasons was noted in the latter decade in addition to a decrease in secondary caries, postoperative sensitivity, unsatisfactory marginal adaptation and wear. The overall rates of failure showed little difference, but the causes showed a notable change. This is believed to be a reflection of increased use of composites for larger restorations and possibly changes of material characteristics.