Multifocal ischaemic stroke and myocardial infarction in a woman with occult lung cancer complicated with chronic DIC and thrombotic endocarditis

Ischaemic stroke in thromboembolic mechanism may be a first sign of neoplastic disease, as in the presented case of a 56-year-old woman. Progressive trombocytopenia, anaemia with reticulocytosis and schistocytes in peripheral blood smear, elevated serum LDH activity as well as coexisting myocardial infarction initially suggested Moschcowitz syndrome. However, plasma exchange did not improve her neurological status and D-dimer values increase in subsequent evaluations indicated chronic DIC. At the same time, on transesophageal echocardiography, thrombotic endocarditis was diagnosed. Screening for cancer showed high CA 125 marker and chest computed tomography revealed lung tumor, not visible on earlier chest X-ray. In further treatment she underwent palliative radiotherapy and continued low molecular weight heparin. The neoplastic process had an unfavorable course and she died after four months. The authors point out that in case of multifocal ischaemic stroke and coexistent thrombocytopenia, neoplastic hypercoagulable state and thrombotic endocarditis should be considered.     

神经元蜡样质脂褐质沉积病(NCL)的基因型与表型相关性研究

Objective:Genotype-phenotype associations were studied in 517 subjects clinically affected by classical neuronal ceroid lipofuscinosis (NCL). Methods:Genetic loci CLN1-3 were analyzed in regard to age of onset, initial neurological symptoms, and electron microscope (EM) profiles. Results: The most common initial symptom leading to a clinical evaluation was developmental delay (30%) in NCL1, seizures (42.4%) in NCL2, and vision problems (53.5%) in NCL3. Eighty-two percent of NCL1 cases had granular osmiophilic deposits (GRODs) or mixed-GROD-containing EM profiles; 94% of NCL2 cases had curvilinear (CV) or mixed-CV-containing profiles; and 91% of NCL3 had fingerprint (FP) or mixed-FP-containing profiles. The mixed-type EM profile was found in approximately one-third of the NCL cases. DNA mutations within a specific CLN gene were further correlated with NCL phenotypes. Seizures were noticed to associate with common mutations 523G>A and 636C>T of CLN2 in NCL2 but not with common mutations 223G>A and 451C>T of CLN1 in NCL1. Vision loss was the initial symptom in all types of mutations in NCL3. Surprisingly, our data showed that the age of onset was atypical in 51.3% of NCL1 (infantile form) cases, 19.7% of NCL2 (late-infantile form) cases, and 42.8% of NCL3 (juvenile form) cases.Conclusion:Our data provide an overall picture regarding the clinical recognition of classical childhood NCLs. This may assist in the prediction and genetic identification of NCL1-3 via their characteristic clinical features.     

The role of social support in the quality of life after stroke. A review of selected experimental research

Surviving of a stroke may be considered as a major stressful life event. Neurological and functional deficits often lead to a loss of independence, social alienation, depression and deterioration of the quality of life. Earlier correlational studies have shown that social support may mediate responses to stroke and improve patients' quality of life. The aim of this article was to review randomized controlled trials (RCTs) concerning the role of professional social support in the quality of life after stroke. The vast majority of the RCTs published in the last decade did not show any positive impact of support on the psychosocial consequences of a stroke. It does not mean, however, that professional support is necessarily ineffective. The reviewed RCTs may fail to detect benefits because of some methodological and theoretical limitations. There is a need of further research but more attention should be given to a power analysis, selection of an appropriate outcome measure and standardisation of a study procedure. It is also important to found research deliberately on existing social support theories.     

Midwifery provision and uptake of maternity care in Indonesia

Objectives To examine the association between midwife density, other characteristics of midwifery provision and village contextual factors, and the percentage of births attended by a health professional and deliveries via caesarean section in two districts in West Java, Indonesia. Methods Analysis of: (i) a census of midwives; (ii) a population‐based survey of women who had delivered over a 2‐year period; (iii) a census of all caesareans in the four hospitals serving the two districts; and (iv) data from National Statistical Office. Results At an average density of 2.2 midwives per 10 000 population, 33% of births are with a health professional, and 1% by caesarean section. Having at least six midwives per 10 000 population was associated with a fourfold increase in caesareans [adjusted risk ratio (RR) 4.3: 95% confidence interval (CI): 3.3–5.5] and a threefold increase in the odds of having a health professional attend the delivery [adjusted odds ratio (OR) 2.88: 95% CI: 0.96–8.70]. The assigned midwife’s professional status and the duration of her service in the village were also associated with higher rates of health professionals’ attendance of delivery and caesareans. Regardless of the provision of services, women’s education and wealth were strong predictors of delivery with a health professional. Conclusions Promoting a stable workforce of midwives, better financial access for the poor and expanding female education are important for the achievement of the fifth Millennium Development Goal (MDG‐5).     

Sulodexide for hemodialysis anticoagulation in heparin-induced thrombocytopenia type II

Heparin-induced thrombocytopenia type II (HIT II) is an immune-mediated prothrombotic state. It requires cessation of all forms of heparin exposure. In maintenance hemodialysis (HD) patients, alternative anticoagulants (i.e. bivalirudin, danaparoid, fondaparinux) may be tried for HD procedure anticoagulation. Sulodexide (SLX) - a purified glycosaminoglycan preparation (80% heparan sulfate and 20% dermatan sulfate) - is not neutralized by platelet factor 4 and may be useful in HIT II. A 32-year-old man on continuous ambulatory peritoneal dilaysis (CAPD) and with protracted atrial fibrillation was given enoxaparin prophylaxis. On day 4, his platelets dropped from 119,000/micronL to 27,000/micronL and HIT II was diagnosed by positive heparin-induced platelet aggregation. While enoxaparin was withdrawn, the platelet count increased and remained stable. In the meantime, atrial fibrillation subsided but the patient developed pseudomonal peritonitis; the catheter was removed and the patient was switched to HD with SLX as an anticoagulant (bolus of 30 mg at HD onset). He was uneventfully treated with HD for 6 weeks and then reverted to CAPD. The widely available and inexpensive SLX may be a new, effective and potentially promising alternative anticoagulant in HD patients with HIT II.     

The short term exposition of AgNO3 on 3T3 mouse fibroblasts cell line

There is an increasing interest in using of silver coated (silver nitrate, silver alloy, silver oxide) catheters for hospital patients. Clinical trials with silver-coated urinary catheters have shown conflicting results. The most often performed catheterization is for a short period of time. The above observations have encouraged the authors to investigate the influence of silver nitrate (AgNO3) on 3T3 fibroblasts viability in vitro during a short time experiment (3 and 12 h). 3T3 fibroblast culture was established. The influence of AgNO3 on the viability of murine 3T3 fibroblasts with the use of trypan blue staining was evaluated. The regression curves and lethal concentrations for 90, 50 and 10% viability were calculated. The lethal concentrations of AgNO3 after 3 h exposition were as follows LC10=0.98, LC50=6.44 and LC90=21.38. The lethal concentrations of AgNO3 after 12 h exposition were as follows LC10=1.05, LC50=6.91 and LC90=22.96. The LC values were similar for 3 and 12 h exposure as well. In conclusion, the silver nitrate has the similar toxic effect on 3T3 fibroblasts during the short and long exposition. Attention should be paid when catheter has a close contact to injured urothelium even for a short period of time.     

Structural and functional characteristic of a model for deep-seated lacunar infarct in rats

Deep-brain lacunar infarct represents a significant clinical problem as it produces severe symptoms highly resistant to rehabilitation. The limited area of necrosis may facilitate neurorepair via the action of various novel neuroprotective strategies including cell-based therapies. The lesion was induced by stereotactic injection of ouabain into adult rat brains. Subsequent behavioral testing involved beam walking task, rotarod, visual discrimination task and apomorphine rotation. For morphological and topographical analysis brain slices were stained with H-E and evaluated under light microscopy. Lesion size was measured in absolute terms and in relation to the whole brain volume. Immunohistochemical analysis for the co-localization of BrdU with specific cell-type markers (PSA-NCAM, NG2, beta-tubulin III, GFAP, ED1) have has been performed, to determine the fate of newly generated cells with emphasis on evidence of neurogenesis. The lesion involved the basal ganglia, basal forebrain nuclei, internal capsule and striatum (just 1-2% of total brain volume). Significant and relatively stable behavioral deficits were observed up to 30 days. Furthermore, large numbers of cells are seen to be newly generated in response to injury with a significant proportion of these being present on account of neurogenesis.     

Assessment of rest tremor in Parkinson's disease

BACKGROUND AND PURPOSE: Rest tremor is the most frequent sign of Parkinson's disease (PD) after bradykinesia, occurring with various severity in about 75% of patients. An objective assessment of rest tremor is difficult. The aim of the study was to analyze rest tremor in PD with the three-dimensional gauging system CMS 10; more specifically, the impact of levodopa treatment on rest tremor, the influence of clinical factors, and the correlation between rest tremor and clinical scales were assessed. MATERIAL AND METHODS: Ninety-five patients with PD (mean age 67.6 years) and 30 healthy people in a control group (mean age 59.3 years) were examined. Clinical scales (UPDRS, Hoehn and Yahr, Schwab and England, as well as Webster scale) were used to assess severity of PD. The assessment of rest tremor was performed within the more and less affected upper limb with the three-dimensional gauging system CMS 10 (Zebris GmbH) before and 1-2 hours after levodopa intake. Frequency (Hz), amplitude (deg), velocity (deg/ms) and acceleration (deg/s2) of the tremor were evaluated. Results were compared with averaged results for left and right upper limb in the control group. RESULTS: The method used in this study objectively showed asymmetry in rest tremor. After levodopa intake, all evaluated parameters of rest tremor were decreased (mainly the amplitude and frequency, and to a lesser degree, velocity and acceleration). The motor part of UPDRS showed the best correlation with rest tremor. CONCLUSIONS: The three-dimensional measuring system CMS 10 is useful in the objective assessment of rest tremor in PD. Rest tremor in PD is under the influence of PD form, the intake of levodopa dose, the amount of levodopa, gender and level of education.     

Different effects of enoxaparin and unfractionated heparin on some thrombogenesis markers during hemodialysis: a cross-over study

Background

Unfractionated heparin (UFH) and low molecular weight heparin constitute fundamental anticoagulants during hemodialysis (HD). We aimed to investigate the effect of UFH and enoxaparin on plasma levels of prothrombin fragment 1 + 2 (PF 1 + 2) and thrombin/antithrombin complex (TAT) as markers of intravascular thrombogenesis during HD.

Methods

We enrolled 22 chronic HD patients, who were randomly assigned to either iv enoxaparin (n = 11) or UFH (n = 11) anticoagulation, and followed prospectively for 12 weeks before crossing over to the alternate therapy for further 12 weeks. Plasma levels of PF 1 + 2 and TAT were measured by immunoassay at the start, at 10 and 180 min of HD session after each period of evaluation.

Results

The baseline PF 1 + 2 and TAT levels were comparable under enoxaparin and UFH treatment. PF 1 + 2 significantly decreased during both UFH (χ² ANOVA = 9.82, P = 0.007) and enoxaparin (χ² ANOVA = 29.40, P < 10^− 6) anticoagulated HD, while over-HD TAT levels changes differed depending on the type of heparin. The switch from enoxaparin to UFH treatment was connected with a significantly higher PF 1 + 2 after 10 and 180 min as well as higher TAT concentration after 180 min of HD. Only during enoxaparin anticoagulated HD 34% PF 1 + 2 decrease and TAT levels after 180 min of HD was closely associated with heparin dosage.

Conclusion

Single bolus of enoxaparin ensures efficient and convenient anti-thrombotic protection during HD procedure. Enoxaparin mean dose of 0.67 mg/kg, which is generally lower than manufacturer's instructions, can be recommended for over-dialytic regular use.     

Progress in the discovery and development of glutamate carboxypeptidase II inhibitors

During the past 10 years, substantial progress has been made in the discovery and development of small molecule glutamate carboxypeptidase II (GCP II) inhibitors. These inhibitors have provided the necessary tools to investigate the physiological role of GCP II as well as the potential therapeutic benefits of its inhibition in neurological disorders of glutamatergic dysregulation. This review article details key GCP II inhibitors discovered in the last decade and important findings from preclinical and clinical studies.