Hagosa D. Abraha

Serum S-100 Protein, Relationship to Clinical Outcome in Acute Stroke

The clinical significance of serum S-100 protein, a protein released by damaged brain tissue, was assessed in patients with acute ischaemic or haemorrhagic stroke and matched controls. Serum S-100 protein concentration was significantly elevated in patients with ischaemic stroke [median (SQR): 0·27 (0·09) μg/L, n = 68] and haemorrhagic stroke [0·43 (0·23) μg/L, n = 13] compared to controls [0·11 (0·03) μg/L, n = 51, P<0·0001]. Although patients with haemorrhagic stroke had higher serum S-100 concentrations compared to patients with ischaemic stroke, this was not quite statistically significant. Serum S-100 concentrations were related to infarct size, large (total anterior circulation) infarcts concentrations having the highest [0·40 (0·22) μg/L], and small vessel (‘lacunar’) infarcts concentrations having the lowest [0·20 (0·06) μg/L, P<0·0005] concentrations. S-100 protein concentration was also significantly related to clinical outcome at three months measured using three disability and handicap scales (n = 81): modified Barthel index (r s=–0·285, P = 0·01), modified Rankin score (r s = 0·313, P = 0·004) and Lindley score (r s = 0·262, P = 0·018) with high values associated with poor clinical outcome. Similarly high values of serum S-100 protein were observed in patients who died or were discharged to an institution [median (SQR): 0·63 (0·29) μg/L and 0·37 (0·13) μg/L, respectively] compared to those who were discharged home [0·26 (0·11) μg/L, P = 0·13]. The present study suggests measurement of serum S-100 protein could be a useful prognostic marker of clinical outcome in acute stroke. Whether S-100 concentrations can be altered by therapeutic intervention in acute stroke remains to be elucidated. Indexing terms: acute stroke/serum S-100/Barthel index/Rankin scale.

Measurement of Markers of Osteoclast and Osteoblast Activity in Patients with Acute and Chronic Diabetic Charcot Neuroarthropathy

Excess osteoclast activity is believed to be responsible for the early bone changes associated with Charcot neuroarthropathy in diabetes mellitus. Markers of osteoclast and osteoblast activity were measured in four groups of patients: 16 with an acute Charcot foot, 16 with a chronic Charcot foot, 10 diabetic controls, and 10 non‐diabetic controls. Serum carboxyterminal telopeptide of type 1 collagen (1CTP), a marker of osteoclastic bone resorption, was significantly raised in the dorsal venous arch of the acute Charcot foot, 6.1 ± 1.5 μg l−1 (mean ± SD) compared with the chronic Charcot foot 4.1 ± 1.4, diabetic controls 3.3 ± 1.4, and non‐diabetic controls 2.8 ± 1.4, p < 0.0001. This local increase in 1CTP was also reflected systemically in a study subgroup of 6 patients with acute Charcot neuroarthropathy, in whom peripheral antecubital vein 1CTP was 9.2 ± 2.6 compared with 9.0 ± 3.1 in the foot. In 6 chronic Charcot neuroarthropathy patients, foot (3.8 ± 1.3) and systemic (4.0 ± 1.5) 1CTP values were similar. Serum procollagen carboxyterminal propeptide (P1CP), an indicator of osteoblastic bone formation, was not significantly different between the feet of patients with acute Charcot neuroarthropathy 112 ± 1.5 μg l−1, patients with chronic Charcot neuroarthropathy 109 ± 1.5 μg l−1, diabetic controls 93.5 ± 2.3 μg l−1, and non‐diabetic controls 90.1 ± 1.5 μg l−1. These results suggest that the acute Charcot foot demonstrates excess osteoclastic activity without concomitant increase in osteoblastic function. This may be important in its pathogenesis. © 1997 John Wiley & Sons, Ltd.

Prediction of cognitive dysfunction after resuscitation from out-of-hospital cardiac arrest using serum neuron-specific enolase and protein S-100

Background: More than 50% of patients initially resuscitated from out-of-hospital cardiac arrest die in hospital. Objective: To investigate the prognostic value of serum protein S-100 and neuron-specific enolase (NSE) concentrations for predicting (a) memory impairment at discharge; (b) in-hospital death, after resuscitation from out-of-hospital cardiac arrest. Methods: In a prospective study of 143 consecutive survivors of out-of-hospital cardiac arrest, serum samples were obtained within 12, 24–48 and 72–96 hours after the event. S-100 and NSE concentrations were measured. Pre-discharge cognitive assessment of patients (n = 49) was obtained by the Rivermead Behavioural Memory Test (RBMT). The relationship between biochemical brain marker concentrations and RBMT scores, and between marker concentrations and the risk of in-hospital death was examined. Results: A moderate negative relationship was found between S-100 concentration and memory test score, at all time points. The relationship between NSE and memory test scores was weaker. An S-100 concentration >0.29 μg/l at time B predicted moderate to severe memory impairment with absolute specificity (42.8% sensitivity). S-100 remained an independent predictor of memory function after adjustment for clinical variables and cardiac arrest timing indices. NSE and S-100 concentrations were greater in patients who died than in those who survived, at all time points. Both NSE and S-100 remained predictors of in-hospital death after adjustment for clinical variables and cardiac arrest timing indices. The threshold concentrations yielding 100% specificity for in-hospital death were S-100: 1.20 μg/l (sensitivity 44.8%); NSE 71.0 μg/l (sensitivity 14.0%). Conclusions: Estimation of serum S-100 concentration after out-of-hospital cardiac arrest can be used to identify patients at risk of significant cognitive impairment at discharge. Serum S-100 and NSE concentrations measured 24–48 hours after cardiac arrest provide useful additional information.

Serum S100β protein as a marker of disease activity in patients with malignant melanoma

The purpose of the study was to evaluate serum S100β protein as a marker of disease activity in patients with malignant melanoma (MM) and compare it with serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). One hundred sixty-four patients with MM, stages I–IV according to the American Joint Committee on Cancer (AJCC), were studied. Recurrent disease was categorized as active (AD) if metastases were evident clinically or with imaging investigations and inactive (ID) if no metastases were apparent at the time of sample collection. The sensitivity and specificity of S100β, LDH, and ALP for discrimination between AD and ID were calculated using receiver-operating characteristic curve (ROC) analysis. Serum S100β, LDH, and ALP concentrations were significantly higher in AD compared to ID. Serum S100β protein was the best discriminator between AD and ID, the areas under the ROC curve being 0.89, 0.71, and 0.70 for

Dissociation of Bone Turnover in Anorexia Nervosa

100β, LDH, and ALP, respectively. Serum S100β and LDH levels (both p<0.0001) and serum ALP levels (p=0.0014) corresponded with the number of metastatic sites involved. Using a cutoff point of 0.20 µg/L for serum S100β protein, a specificity of 93% with a sensitivity of 68% was obtained for AD in MM. In stage IV disease, S100 was an independent predictor of survival in univariate (p=0.001; hazard ratio=1.0156) and multivariate (p=0.038; hazard ratio=1.0108) analyses. Serum S100β protein is a better indicator of disease activity in MM than LDH or ALP and is an independent predictor of survival in stage IV disease.

Bone mineral density and height gain in children with chronic cholestatic liver disease undergoing transplantation.

Biochemical markers were measured to assess bone turnover in a cross-sectional study of 43 patients with anorexia nervosa; 28 were at their first assessment (untreated) with a body mass index (BMI) (median interquartile range) of 13·3 (2) kg/m2. A second group of 15 patients undergoing treatment (treated) had a median BMI of 17·6 (2·8) kg/m2. The median, interquartile range of urinary deoxypyridinoline (DPyd), a bone resorption marker, was raised in both groups compared with an age-matched control population [DPyd = 17·8 (15·2), 17·5 (16·4) and 9·2 (4·0) nmol/mmol creatinine, respectively]. Serum type 1 collagen carboxyterminal propeptide (P1CP), a marker of bone formation, was similar to controls in the untreated patients [112 (29) and 112 (78·5)ng/ml, respectively], but was significantly raised in the treated patients [163 (219)ng/ml, P < 0·05]. A second group of 21 patients was followed prospectively, on admission and during 8 weeks of intensive inpatient care (BMI on admission and after 8 weeks was 13·0 (2) and 16·7 (3) kg/m2, respectively). The resorption marker, serum type 1 collagen carboxyterminal telopeptide (1CTP) was raised on admission and remained high during treatment. P1CP and osteocalcin levels were similar to control levels on admission but increased with treatment, and after 8 weeks were 40% and 63% higher respectively than on admission. These findings suggest that in untreated anorexia nervosa there was uncoupling of bone turnover as bone resorption markers were raised without a concomitant increase in bone formation markers. As the condition was treated and patients gained weight, the formation markers also increased, leading to a more balanced, although higher, bone turnover.

Evaluation of serum markers of neuronal damage following severe hypoglycaemia in adults with insulin-treated diabetes mellitus

Background. Osteodystrophy is a well-described complication of chronic liver disease. Previous reports in adults and children undergoing liver transplantation (LT) were discordant, with the former showing no improvement of bone disease in the first year after transplantation and the latter demonstrating remarkable benefit from it. Our aim was to perform a pilot study on osteodystrophy in children undergoing LT and evaluate the contribution of growth on bone mineral density (BMD) changes. Methods. We studied six patients (two male), with a median age at transplantation of 8.8 (range 3.8–16.6) years. Indications for transplantation were biliary atresia and progressive familial intrahepatic cholestasis (three patients each). BMD was studied with dual-energy x-ray absorptiometry and biochemical markers of liver and bone function in patients before and at 3, 6, and 12 months after LT. Results. Median L2-L4 spinal BMD was 0.54 g/cm2 (range 0.29–0.87) before LT, and 0.58 g/cm2 (0.27–0.86) at 3 months, 0.66 g/cm2 (0.36–1.00) at 6 months, and 0.76 g/cm2 (0.44–1.02) at 12 months after LT (P =0.005). Median height was 133 (range 93–167) cm before LT, and 134 (93–167) at 3 months, 136 (97–167) at 6 months, and 139 (102–167) at 12 months after LT. There was direct correlation between height gain and total body BMD improvement (r =0.929, P =0.007). Conclusion. BMD in children with chronic cholestatic liver disease improves remarkably by 12 months after LT. Catch-up growth in children can account for the different effect of LT on bone density between adult and pediatric populations in the first year after surgery.

Serum S-100β protein is a potential biochemical marker for cerebral oedema complicating severe diabetic ketoacidosis

Neurone‐specific enolase (NSE) and protein S‐100 (S‐100) may be used as markers of acute neuronal damage in humans with neurological disorders.

Diurnal, Week-to-Week, and Long-Term Variation in Urine Deoxypyridinoline Cross-Link Excretion in Healthy Older Women

CASE REPORT A 39-year-old man with Type 1 diabetes mellitus was hospitalized with severe diabetic ketoacidosis (DKA). Sixteen hours after admission he suddenly deteriorated having a respiratory then cardiac arrest. A brain computed tomography scan performed 2 h after the respiratory arrest showed severe cerebral oedema. Serial serum samples were stored and analysed for S-100beta protein. The S-100beta protein concentration was initially normal (0.12 microg/l) then rose significantly before the onset of the respiratory arrest (8.5 h = 0.61 microg/l, 14.5 h = 0.9 microg/l, 18 h = 1.6 microg/l, 25.5 h = 3.1 microg/l, 34 h = 4.6 microg/l and44 h = 19.5 microg/l). CONCLUSIONS In this case of DKA, serum S-100beta concentration rose coinciding with the onset of cerebral oedema, before it became clinically evident. Monitoring serum S-100beta may have a useful role in the management of DKA.

Serum S100 protein as a marker of disease activity in patients with malignant melanoma

OBJECTIVES: To establish a reference range for morning and afternoon excretion of urinary deoxypyridinoline (DPD) in apparently healthy older women selected from a volunteer database. To assess the extent of diurnal variation and short and long‐term within‐subject longitudinal variation.