Identification of a predominant cognitive phenotype in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Cognitive impairment occurs frequently in multiple sclerosis (MS). However, the prevalence and clinical characteristics of cognitive MS phenotype are not well established. The aim of the study was to characterize the clinical course and neurocognitive impairment of patients with MS meeting an Expanded Disability Status Scale (EDSS)-defined cognitive phenotype. METHODS: A total of 2302 patients from the Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women's Hospital (CLIMB) study were studied. Predominant cognitive MS phenotype was defined as EDSS Cerebral Functional System (FS) subscore ≥3 and remaining EDSS FS subscores ≤2 on at least one clinical visit. Demographic/clinical characteristics, phenotype stability and neurocognitive domain impairment of these subjects were assessed. RESULTS: A total of 60 of 2302 (2.6%) patients (age 52.8 ± 10.8 years, 68% female, 82% relapsing MS) met criteria for phenotype designation. A total of 29 of 60 (48%) were designated within 10 years of their presenting MS symptom. The mean cohort annualized relapse rate was 0.38 and EDSS score at last clinical assessment was 3.2 ± 1.3. Cognitive phenotype status was poorly sustained, with only 27% of subjects maintaining Cerebral FS score ≥2 throughout all follow-up. However, predominant cognitive phenotype subjects with clinical neuropsychiatric testing [n = 39/60 (65%)] frequently had cognitive impairment (1.5 SD below mean) in ≥1 domain [n = 30/39 (77%) of subjects] affecting memory, attention/executive function and processing speed. A total of 11 of 39 (28%) patients had severe-range cognitive impairment (3.0 SD below mean). Cognitive phenotype designation was associated with low rate of employment at last clinical assessment. CONCLUSION: Predominant cognitive MS phenotype is rare, although an EDSS-based definition identifies patients with multidomain cognitive impairment and may serve as a practical screen for identification of patients who might warrant close monitoring of neurocognitive status.

Morphological assessment of thin basement membrane disease.

Thin basement membrane disease is more common than IgA nephropathy or Alport syndrome, which are also associated with the presence of erythrocyturia. Very few reports on the disorder are available in the Polish literature. The objective of this work was to analyze the results from 83 patients with thin basement membrane syndrome as well as to formulate a proposal of strict morphological assessment criteria for the disorder. Attention was drawn to the requirement of thickness of the lamina densa rather than the entire basement membrane thickness and a sufficiently high number of loops featuring thinned lamina densa, namely at least 80% of loops, being taken into account. Occurrence of other morphological changes associated with the disorder and clinical symptoms other than erythrocyturia was also highlighted.

IL-6, TNF-alpha, IL-1-beta arterial wall expression is independent of serum concentration in patients sustaining primary or secondary open vascular reconstructions.

AIM: The aim of this study was to assess morphological and immunohistochemical differences in arterial wall inflammation during primary and secondary vascular reconstructions. METHODS: Forty patients with lower extremities ischemia underwent vascular reconstruction: Group I included patients undergoing primary vascular reconstruction with 25 minor arterial reconstructive procedures; Group II included patients undergoing secondary reconstruction due to limb ischemia after at least 12 months since first operation (15). Immunohistochemical expression of IL-1-BETA,IL-6,and TNF-alpha in arterial wall was correlated with serum concentration. RESULTS: No differences were observed in IL-1-beta, IL-6, TNF-alpha expression among groups (P=0.06, P=0.13, P=0.9). Cytokines expression was not accompanied by the growth of its serum concentrations (P=0.8, P=0.9). IL-6 serum concentration depended on the degree of limb ischemia and was very high in case of critical limb ischemia (P=0.006). Arterial morphology was comparable among the groups. CONCLUSION: IL-6, IL-1-BETA, TNF-alpha expression in the arterial wall is comparable in primary and secondary lesions. Serum concentrations of IL-6, IL-1-BETA, TNF-alpha are independent of its arterial wall expression.

[Rare case of the cervical vagal neurinoma]. / Rzadki przypadek nerwiaka odcinka szyjnego nerwu blednego.

Neurinoma is the most common tumor of the neurogenic origin. Primary location in the neck with the vagal nerve as a source is very rare clinical situation (less than 100 cases published in the literature). The authors would like to present a case of 35 old men with vagal neurinoma. Main symptoms included painless neck tumor found on palpation. Differential diagnosis included the pedicled cyst and metastatic neck mass. The ultrasound picture was unclear. The intraoperative findings suggested the tumor arising from the vagal nerve. In first day after the surgery hoarseness appeared with paresis of the right vocal cord in the examination. The final histological evaluation revealed neurinoma.

Prognostic significance of augmented metallothionein (MT) expression correlated with Ki-67 antigen expression in selected soft tissue sarcomas.

In soft tissue sarcomas, the most important prognostic criteria include extent of malignancy (G), size of the tumour and intensity of Ki-67 antigen expression. In recent times expression of metallothionein (MT) in cells of some malignant processes of epithelial origin was found to correlate with intensity of Ki-67 antigen expression and to carry a possible prognostic significance. The present study aimed at a demonstration of prognostic value of MT expression and at comparing it with Ki-67 antigen expression and G grade in selected soft tissue sarcomas. Immunohistochemical studies were performed on paraffin sections in 54 cases of malignant fibrous histiocytoma (MFH), 18 cases of liposarcoma and 20 cases of synovial sarcoma. The extent of MT and Ki-67 antigen expression was evaluated and an attempt was made to correlate the results with each other and with grade of the tumour. Expression of MT was evident both in the cytoplasm and in cell nuclei of all studied sarcomas. The most pronounced MT expression was noted in MFH-type tumours. The extent of Ki-67 antigen expression was similar in MFH and liposarcoma and was the lowest in synovial sarcoma. In MFH, liposarcoma and synovial sarcoma a pronounced positive correlation was documented between expression of MT and Ki-67 antigen (r=0.85; p<0.001; r=0.93, p<0.0001; r=0.79, p<0.0001). In all types of the tumours a positive relation was detected between MT expression, expression of Ki-67 and G grade of malignancy in the tumour. Moreover, patients with higher MT expression in the studied tumours demonstrated a shorter survival. MT expression in soft tissue tumours of MFH, liposarcoma and synovial sarcoma type strongly correlated with intensity of proliferation (Ki-67) and G grade and could be useful in defining the extent of malignancy and in prognostic appraisal in the tumours.

Chain reaction cloning: a one-step method for directional ligation of multiple DNA fragments.

A novel DNA assembly method, chain reaction cloning (CRC), is described. CRC enables the ordered assembly of multiple DNA fragments in a single step. The power of the technique was demonstrated by the directed in vitro assembly of a plasmid comprised of six DNA fragments from a pool of 12 available fragments. The odds of obtaining the correct plasmid clone in a single step, using conventional techniques, is less than 1 in 191000000. Using CRC, the desired plasmid was recovered at a frequency of one in two. Ligation is no longer the rate limiting step in cloning, and limitless possibilities exist for the reconstruction of complex genomes.

Pregnancy outcome after maternal poisoning with brodifacoum, a long-acting warfarin-like rodenticide.

BACKGROUND: Brodifacoum is a potent warfarin-like anticoagulant used in many rat-poisoning products. Its availability has led to several reported human ingestions, none previously reported in pregnancy. CASE: A woman presented at 22 weeks' gestation in hemorrhagic diathesis, attributed to the ingestion of rat poison containing brodifacoum several days earlier. Aggressive vitamin K therapy controlled the maternal coagulopathy, and no fetal hemorrhage was observed by sonography. Her subsequent prenatal course and delivery were unremarkable, and she was delivered of a healthy infant, who has remained well for at least 1 year. CONCLUSION: In this patient, brodifacoum ingestion in pregnancy caused substantial maternal hemorrhage, but no fetal hemorrhage or teratogenic effects were observed.

Functional assessment of joint use in experimental inflammatory murine arthritis.

A select group of cartilage proteoglycans (fetal human, porcine, and canine articular cartilages and human osteophytes, all depleted of chondroitin sulfate) produces progressive polyarthritis and spondylitis in BALB/c mice. The development of the disease in this murine strain is dependent on the expression of both cell-mediated and humoral immunities to host mouse cartilage proteoglycan. Autoantibodies have been detected in sera of arthritis animals from the fifth to sixth week after immunization, and their appearance precedes the development of the first clinical symptoms by a few days in animals with passively transferred arthritis. In this preliminary experiment, we describe several functional tests and gait analyses in normal mice, in acutely and chronically arthritic mice, and in randomly selected mice with proteoglycan-induced and collagen-induced arthritis. The procedures revealed that changes in joint use and gait could predate by weeks the appearance of the first clinical symptoms (joint swelling, redness, and joint stiffness) of arthritis in mice. Moreover, abnormalities measured by functional tests, such as strength of grip and maintenance of posture on sandpaper, wood, or vinyl surfaces at three different tilt angles (30, 45, and 60 degrees), and gait analysis preceded the appearance of autoantibodies in sera of immunized animals; this indicates that such measurements could provide a noninvasive and simple method to assess joint function accurately during the development of arthritis.

Improved codistillation method for determination of carbon tetrachloride, ethylene dichloride, and ethylene dibromide in grain and grain-based products.

A method is described for the determination of the common fumigants carbon tetrachloride (CCl4), ethylene dichloride (EDC), and ethylene dibromide (EDB) in grain and grain-based products. A properly prepared sample is mixed with water and hexane, an internal standard mixture of 1,2-dichloropropane (DCP) and 1,2-dibromopropane (DBP) is added, and the fumigants are codistilled with the hexane into an appropriate receiver. After the hexane solution is dried over sodium sulfate, the quantities of fumigants present are quantitated on a gas chromatograph (GC) equipped with an electron capture detector (ECD). For the matrices investigated, the relative standard deviation of the method was 6.0, 9.7, and 23.1% for CCl4, EDC, and EDB, respectively. Recoveries of added fumigants were 107, 95, and 101%, respectively. Comparison with an acetone-water soak extraction method gave a correlation of 0.967 between methods for EDB with odds of a difference between methods of 35%.