Early prediction of functional outcome one year after initial unilateral hemispheric stroke]

BACKGROUND AND PURPOSE: Several prognostic factors have been identified for outcome after stroke. We conducted a study to determine early predictive factors of functional outcome one year after stroke and to evaluate which factors are independent predictors, with an aim of specifying the role of age, aphasia, unilateral neglect, cognitive impairment and family social support. METHODS: Observational cohort study of 156 patients. All patients admitted to the university hospital for initial unilateral hemispheric stroke were included. The study duration was two years (inclusion, one year, and follow-up, one year) .The initial evaluation of stroke was conducted at day 2 and day 15 and included the Motricity Index and Trunk Control Test, New Functional Ambulation Classification, Frenchay arm test, Mini-Mental State Examination, Boston Diagnostic Aphasia Examination, unilateral neglect evaluation, and depression. Data on functional recovery (Barthel Index) were collected at day 360. RESULTS: The average age of patients was 72 years. Age was correlated to social situation (P<0.01) and previous neurological impairment (P<0.01). A multiple regression analysis, including 14 initial clinical factors correlated with the Barthel Index score at day 360, revealed 4 independent early predictive factors of outcome: initial score of Barthel Index at day 2 and its progression from day 2 to day 15, disorders of the executive functions and previous neurological impairment. CONCLUSION: In our cohort, in accordance with previous studies, age, cognitive impairment, unilateral neglect, aphasia, depression and social situation are not independent factors of poor outcome after stroke as evaluated by the Barthel Index.     

Amino acid metabolism during platelet storage for transfusion

Previous studies indicated that the concentration of ammonia rises during storage of platelet concentrates (PC) at 22 degrees C for transfusion and that fuels other than glucose are important for metabolism. Therefore, in the current study, we measured the concentrations of 17 plasma amino acids during PC storage; 16 of these either rose or were unchanged while the concentration of glutamine fell to zero by day 4. As the concentration of glutamine fell, the concentration of glutamate rose with a relationship suggesting that 65-75% of the glutamine was metabolized no further than glutamate. Phosphate-dependent glutaminase activity was present in platelets at 22.3 +/- 6.3 nmol/min/mg protein, a level similar to that seen in lymphocytes and macrophages. Leucodepletion studies excluded a significant contribution of contaminating leucocytes to these measurements. Thrombin stimulation did not increase the rate of glutamine metabolism. Analysis of the rates of glutamine metabolism suggests that it accounts for most of the ammonia produced during PC storage. However, it appears to be relatively insignificant as a metabolic fuel. The role of glutamine metabolism for platelets is uncertain. It may be a vestige of a pathway in the megakaryocyte. The ammonia which it produces may be deleterious for platelets and for patients with liver disease who receive PC infusions.     

Measurement of serum acetaminophen-protein adducts in patients with acute liver failure

BACKGROUND & AIMS: Acetaminophen toxicity is the most common cause of acute liver failure (ALF) in the United States and Great Britain, but may be underrecognized in certain settings. Acetaminophen-protein adducts are specific biomarkers of drug-related toxicity in animal models and can be measured in tissue or blood samples. Measurement of serum adducts might improve diagnostic accuracy in acute liver failure (ALF) patients. METHODS: We measured serum acetaminophen-protein adducts using high-pressure liquid chromatography with electrochemical detection in coded sera of 66 patients with ALF collected prospectively at 24 US tertiary referral centers. Samples were included from 20 patients with well-characterized acetaminophen-related acute liver failure, 10 patients with ALF owing to other well-defined causes, 36 patients with ALF of indeterminate etiology, and 15 additional patients without ALF but with known acetaminophen overdose and minimal or no biochemical liver injury. RESULTS: Acetaminophen-protein adducts were detected in serum in 100% of known acetaminophen ALF patients and in none of the ALF patients with other defined causes, yielding a sensitivity and specificity of 100%. In daily serial samples, serum adducts decreased in parallel with aminotransferase levels. Seven of 36 (19%) indeterminate cases demonstrated adducts in serum suggesting that acetaminophen toxicity caused or contributed to ALF in these patients. Low adduct levels were present in 2 of 15 patients with acetaminophen overdose without significant liver injury. CONCLUSIONS: Measurement of serum acetaminophen-protein adducts reliably identified acetaminophen toxicity, and may be a useful diagnostic test for cases lacking historical data or other clinical information.     

Disc space narrowing as a new risk factor for vertebral fracture: the OFELY study

OBJECTIVE: In a previous cross-sectional analysis, we found a positive association between disc space narrowing (DSN) and vertebral fracture. The aim of the present study was to analyze prospectively the risk of vertebral and nonvertebral fractures in women with spine osteoarthritis (OA). METHODS: Using radiographs, spine OA was evaluated in 634 postmenopausal women from the OFELY (Os des Femmes de Lyon) cohort (mean+/-SD age 61.2+/-9 years). Prevalence and severity of spine OA were assessed by scoring osteophytes and DSN. Incidental clinical fractures were prospectively registered during annual followup, and vertebral fractures were evaluated by radiography every 4 years. RESULTS: During an 11-year followup, fractures occurred in 121 women, including 42 with vertebral fractures. No association was found between osteophytes and the risk of fracture. In contrast, DSN was associated with an increased risk of vertebral fractures but not of nonvertebral fractures. After adjusting for confounding variables, the presence of DSN was associated with a marked increased risk of vertebral fractures, with an odds ratio of 6.59 (95% confidence interval 1.36-31.9). In addition, 95% of incident vertebral fractures were located above the disc with the most severe narrowing. CONCLUSION: This longitudinal study shows that, despite a higher bone mineral density (BMD), women with spine OA do not have a reduced risk of fracture and that DSN is significantly associated with vertebral fracture risk. The location of DSN and of incident vertebral fractures suggests that disc degeneration impairs the biomechanics of the above spine, which leads to the increased risk of vertebral fractures, independent of BMD. We suggest that DSN is a newly identified risk factor for vertebral fracture that should be taken into consideration when assessing vertebral fracture risk in postmenopausal women.     

A polymorphic GT short tandem repeat affecting beta-ENaC mRNA expression is associated with low renin essential hypertension

BACKGROUND: The epithelial sodium channel (ENaC) is a candidate gene associated with the development of essential hypertension. A potentially polymorphic repetitive region (GT dinucleotide short tandem repeat [STR]) was identified in intron 8 of beta-ENaC gene (SCNN1B). The aim of this study was to identify the prevalence and distribution of a polymorphic GT-STR in SCNN1B in Chilean essential hypertensive (EH) patients and to analyze the correlation between the different genotypes with plasma renin activity (PRA) and serum aldosterone (SA), and furthermore, to evaluate the beta-ENaC gene expression in vitro. METHODS: We studied 133 patients with EH and 69 normotensive (NT). In both EH and NT subjects we measured PRA, SA, urine sodium, and genotyped them according to the GT-STR length using sequencing analysis. We detected 11, 13 and 14 GT alleles in EH and NT subjects. Both groups were classified according to genotype: 14/14, 14/13, 13/13, 13/11, and 11/11. Influence of the GT-STR on beta-ENaC minigene expression was evaluated by real-time polymerase chain reaction. RESULTS: In EH, PRA decreased with the length of the STR region 11/13, 1.40 +/- 0.69; 13/13, 1.16 +/- 0.61; 13/14, 0.90 +/- 0.56; 14/14, 0.32 +/- 0.09 ng/mL/h; P < .01. Likewise, PRA in patients with EH with 14/14 or 14/13 genotypes were lower than EH with 13/13 or 13/11 genotypes (0.77 +/- 0.5 v 1.24 +/- 0.6 ng/mL/h; P < .01). Real-time polymerase chain reaction demonstrated an increased beta-ENaC expression in minigenes containing 14 GT-STR. CONCLUSIONS: We have identified a polymorphic GT-STR in the beta-ENaC gene, which is present in the EH and NT Chilean population. Biochemical analysis showed a possible linkage between this polymorphic region and low renin hypertension. The in vitro assay suggests that GT-STR could regulate the beta-ENaC expression.     

经脐单孔腹腔镜技术在治疗双侧精索静脉曲张中的应用

目的探讨经脐单孔腹腔镜精索静脉高位结扎术治疗双侧精索静脉曲张的临床应用价值。方法应用腹腔镜技术对42例双侧精索静脉曲张患者行双侧精索静脉高位结扎术,其中经脐单孔腹腔镜组20例,传统腹腔镜组22例。对比两种手术方式患者术中出血量、保留睾丸动脉情况、手术时间、术后下床活动时间、肠功能恢复时间及患者住院时间等指标;检测患者术前及术后1年的精液质量。分别于术后1、3、6个月和1年对患者进行4次门诊复查,检查切口恢复情况及阴囊、精索、睾丸有无并发症发生,并询问患者阴囊下坠不适等自觉症状的缓解情况。结果两组手术均获成功,无严重并发症发生。经脐单孔腹腔镜组与传统腹腔镜组术中出血量[（5±1）ml和（5±1）ml,t=-0．452,P〉0．05]、手术时间[（41±7）min和（39±3）min,t=0．686,P〉0．05]、术后肠功能恢复时间[（11±1）h和（11±2）h,t=-1．631,P〉0．05]、术后住院时间[（3．1±0．7）d和（3．4＋0．7）d,t=-1．447,P〉0．05],差异均无统计学意义。术后应用止痛药单孔腹腔镜组1例（5．0％）,低于传统腹腔镜组7例（31．8％）,差异有统计学意义（X^2=4．886,P〈0．05）。经脐单孔腹腔镜组切口近于“无瘢痕”。所有病例均于术后1年进行切口满意度问卷调查,两组比较差异有统计学意义（X^2=7．636,P〈0．01）。结论单孔腹腔镜下双侧精索静脉高位结扎术手术效果与传统腹腔镜手术相当,但更加微创,美学效果明显,是腹腔镜手术发展的掐璐．     

Magna-field irradiation and autologous marrow rescue in the treatment of pediatric solid tumors

Marrow ablative therapy has been given to pediatric patients with a variety of disseminated tumors. Eight patients with advanced neuroblastoma received autologous marrow reinfusion after intensive therapy. Three of eight are in continuous complete remission from 7 to 60 months. An additional four patients received allogeneic marrow transplantation and two remain in continuous complete response at 21 and 39 months. Intensive therapy and autologous marrow reinfusion have been applied to Ewing's sarcoma, but only preliminary results are available. Six patients with disseminated rhabdomyosarcoma and extra-osseous Ewing's sarcoma received conventional chemotherapy followed by sequential hemi-body irradiation. Four of six patients received autologous marrow rescue. Their median disease-free survival is 17 months. This preliminary experience demonstrates the feasibility of using marrow ablative therapy with autologous marrow transplantation in the treatment of pediatric solid tumors. Continuing Phase II studies are required to substantiate its efficacy.     

Short communication: possible association of newly absorbed serotonin with nonmetabolic, granule-located adenine nucleotides in human blood platelets

[3H]-adenine-labeled human platelets in plasma were incubated with or without nonradioactive serotonin. Release reaction was then induced by ADP, epinephrine, collagen, or thrombin. Platelets that had been incubated with serotonin released four times as much serotonin as platelets incubated without serotonin. The specific radioactivities of the ATP and ADP released to plasma during release reaction induced with all four inducers were the same in both systems. This shows that when serotonin is taken up by human platelets, it enters the compartment containing nonmetabolic, granula-stored ATP, and not the compartment with metabolic extragranular ATP. These results suggest that the mechanism of serotonin storage in human platelets is similar to that in other species investigated, i.e., rabbit, guinea pig, and pig.     

Potentiation between intracellular cyclic-AMP-elevating agents and inducers of leukemic cell differentiation

Acute leukemia is the result of a defect in the process of normal cellular differentiation. Human leukemia cell lines (HL60, RDFD-2) have been established which can be induced to differentiate into phenotypically mature cells by a variety of agents. Recent evidence suggests that cyclic adenosine 3'-5'-monophosphate (cAMP) and the cAMP dependent protein kinase (cAMP-dPK) may be intimately involved in myeloid differentiation. The addition of low levels of a wide variety of inducers of a diverse chemical nature, dimethylformamide (DMF), retinoic acid (RA), actinomycin D (ACT-D) or hypoxanthine (HPX) prior to the addition of 8-bromo-cyclic adenosine 3'-5' monophosphate (8-Br-cAMP), cholera toxin (CT) or the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) results in marked potentiation of differentiation of both HL60 and RDFD cells as manifested by the acquisition of the antigen OKM-1, the ability to reduce nitroblue tetrazolium or expression of the chemotactic receptor. Potentiation of differentiation is also observed when 8-Br-cAMP, CT or IBMX is added prior to the addition of either RA, DMF, ACT-D or HPX. These results suggest a role for cAMP in myeloid differentiation.