Therapeutics for multiple sclerosis symptoms

Symptoms management in multiple sclerosis is an integral part of its care. Accurate assessment and addressing the different symptoms provides increased quality of life among patients with multiple sclerosis. Multiple sclerosis symptoms may be identified as primary, secondary, or tertiary symptoms. Primary symptoms, such as weakness, sensory loss, and ataxia, are directly related to demyelination and axonal loss. Secondary symptoms, such as urinary tract infections as a result of urinary retention, are a result of the primary symptoms. Tertiary symptoms, such as reactive depression or social isolation, are a result of the social and psychological consequences of the disease. Common multiple sclerosis symptoms include fatigue and weakness; decreased balance, spasticity and gait problems; depression and cognitive issues; bladder, bowel, and sexual deficits; visual and sensory loss; and neuropathic pain. Less-common symptoms include dysarthria and dysphagia, vertigo, and tremors. Rare symptoms in multiple sclerosis include seizures, hearing loss, and paralysis. Symptom management includes nonpharmacological methods, such as rehabilitation and psychosocial support, and pharmacological methods, ie, medications and surgical procedures. The keys to symptom management are awareness, knowledge, and coordination of care. Symptoms have to be recognized and management needs to be individualized. Multiple sclerosis therapeutics include nonpharmacological strategies that consist of lifestyle modifications, rehabilitation, social support, counseling, and pharmacological agents or surgical procedures. The goal is vigilant management to improve quality of life and promote realistic expectations and hope.     

Structured coculture of stem cells and disc cells prevent disc degeneration in a rat model

Background contextHarnessing the potential of stem cells is an important strategy for regenerative medicine. This study explores the use of bilaminar coculture pellets (BCPs) of mesenchymal stem cells (MSCs) and nucleus pulposus cells (NPCs) as a cell-based therapy for intervertebral disc regeneration. Prior in vitro experiments have shown that BCP can help differentiate MSCs and substantially improve new matrix deposition.PurposeTo evaluate the clinical relevance of BCPs by testing the system in vivo.Study design/settingWe have designed a novel spherical BCP where MSCs are enclosed in a shell of NPCs. The pellets were tested in vivo in a rat tail model of disc degeneration.MethodsRat caudal intervertebral discs were denucleated and treated with BCP in a fibrin sealant (FS) carrier (controls were MSCs suspended in FS; NPCs suspended in FS; MSCs and NPCs suspended in FS; FS only; and surgery only). At 14 and 35 days after implantation, the animals were euthanized and discs were evaluated for proteoglycan content, enzyme-linked immunosorbent assay for inflammatory cytokines, cell retention using polymerase chain reaction, disc height, histology, and disc grade based on a blinded scoring system.ResultsThe proteoglycan and cytokine levels were not significantly different among groups. The BCP group had higher cell retention than controls. Disc height and disc grade increased over time only in the BCP group. Bilaminar coculture pellets were the only treatment to show proteoglycan staining in the nucleus space at 35 days.ConclusionsThis study shows that BCPs may prevent postnucleotomy disc degeneration in vivo. Larger animals and longer time points will be necessary to further judge potential clinical impact. As opposed to strategies that require growth factor supplements, predifferentiation, or genetic manipulations, BCPs are a self-sustaining and targeted method for tissue regeneration in situ.     

Apoptotic and cell cycle regulatory markers in uterine leiomyosarcoma

OBJECTIVES: The primary aim of this study was to investigate the expression of apoptotic and cell cycle regulators p53, p21, p27, bax, and bcl-2 in uterine leiomyosarcoma in order to identify molecular pathways that possibly could be important in the development of leiomyosarcoma. A secondary aim was to examine if the apoptotic and cell cycle regulatory protein expression profile of uterine leiomyosarcoma is potentially useful for clinical prognostic purposes. METHODS: A tissue microarray representing 36 uterine leiomyosarcomas and 19 uterine leiomyomas was created with 3 representative cores from each tumor. Immunohistochemical staining was performed for bcl-2, bax, p21, p27, and p53 using standard techniques. Staining was scored 0-12 for each marker, 0-3 being negative and 4-12 positive. Outcome analyses were performed only for leiomyosarcomas. First recurrence was determined from the time of initial diagnosis. Survival was determined from the time of initial diagnosis to last follow-up. RESULTS: Associations were found between disease type (leiomyosarcoma vs. leiomyoma) and the positivity status of p21 (43% vs. 0%, P < 0.001), p53 (54% vs. 0%, P < 0.001), and bax (34% vs. 94%, P < 0.001). bcl-2-positive leiomyosarcoma was associated with a longer time to recurrence (P = 0.02) in a univariate analysis. In a multivariate analysis, tumor stage was the only independent significant prognostic factor (P = 0.002). CONCLUSION: The significant differential expression of apoptotic and cell cycle regulatory proteins in uterine leiomyosarcoma as compared to benign smooth muscle tumors suggests that pathways involving these proteins may be important in the development of malignant disease and, therefore, could be potential targets for molecular therapies.     

Update on alpha-linolenic acid

Consumption of omega 3 fatty acids is known to have health benefits. For many years, the importance of the only member of the omega 3 family considered to be essential, alpha-linolenic acid (ALA), has been overlooked. Current research indicates that ALA, along with its longer chain metabolites, may play an important role in many physiological functions. Potential benefits of ALA include cardioprotective effects, modulation of the inflammatory response, and a positive impact on both central nervous system function and behavior. Recommended levels for ALA intake have been set, yet the possible advantages of its consumption are just being revealed.     

National survey of ophthalmologists in Singapore for the assessment and management of asymptomatic angle closure

PURPOSE: Approximately 10% of Chinese people older than 50 years in Singapore have asymptomatic narrow angles [also termed primary angle closure suspects (PACS)]. The aim of this study was to determine the attitudes and practices of ophthalmologists in Singapore regarding the management of these patients. METHODS: A nation wide questionnaire-based survey was conducted on all registered, practicing ophthalmologists in Singapore by electronic mail and post. An ophthalmologist was defined as a doctor who had completed at least 3 years of specialist training in ophthalmology and had passed the Master's Degree in Ophthalmology or equivalent examinations. The survey asked the ophthalmologists about the methods and criteria used for the diagnosis of angle closure. It also inquired about the management of PACS and opinions on the effectiveness of prophylactic laser peripheral iridotomy (LPI) in preventing both acute and chronic angle closure. RESULTS: A total of 126 out of 158 ophthalmologists responded (79.7% response rate). Of the respondents, 84.9% would advise prophylactic LPI for asymptomatic PACS; 84.9% believed that prophylactic LPI would prevent acute angle closure but only 44% thought that it could prevent the development of glaucomatous optic nerve damage. The preferred method of prophylactic LPI was sequential argon-YAG LPI. In assessing patients for angle closure, 85.4% used gonioscopy, 92.9% assessed anterior chamber depth, and 17.5% performed provocative tests. CONCLUSIONS: Ophthalmologists in Singapore vary in the method of assessment of patients with angle closure. Most believe that prophylactic LPI should be performed for asymptomatic PACS.     

Bronchodilator responsiveness in wheezy infants predicts continued early childhood respiratory morbidity

Objective: Spirometry including bronchodilator responsiveness is considered routine in the workup of asthma in older children. However, in wheezy infants the existence of bronchodilator responsiveness and its prognostic significance remain unclear. Methods: Infants (< 2 years) with chronic or recurrent wheezing or coughing were evaluated by infant pulmonary function testing (PFT). Maximal expiratory flow at the point of functional residual capacity (V?_maxFRC) was measured before and 20 minutes after salbutamol administration. Only infants with an obstructive profile (V?_maxFRC < 80% predicted) were included. The infants were divided into two groups with regard to whether or not a response to salbutamol was observed on PFT. A response was defined as a mean V?maxFRC after salbutamol administration exceeding the upper confidence interval limit of individual pre-bronchodilator V?_maxFRC measurements. Follow-up data was gathered after a mean of 2 years. Measurements and Main Results: Sixty infants were included in the study of which 32 (53%) demonstrated responsiveness to bronchodilators. The infants in the responsive group had a significantly higher frequency of physician visits for wheezing than the non-responders (3.0 mean visits/yr vs. 1.5 respectively, P = 0.03), and had a higher likelihood of having received asthma medication in the last year of the follow-up period (84% vs. 50% respectively, RR: 1.68[1.10–2.56]). At the end of the follow-up period, more parents in the responsive group reported continued respiratory disease (71% vs. 22%, RR:3.21[1.30–7.95]). Conclusions: Bronchodilator responsiveness can be demonstrated by infant PFT in infants with recurrent wheezing and can predict increased respiratory morbidity until 3 years of age.     

Clients undergoing chorionic villus sampling versus amniocentesis: Contrasting attitudes toward pregnancy

We analyzed interview data from 44 primarily white, middle‐class women who had used the prenatal diagnostic technique of chorionic villus sampling (CVS: n = 24) or amniocentesis (n ‐ 20). CVS provides earlier results but carries a somewhat higher risk of miscarriage. Amniocentesis clients were highly committed to the pregnancy and expressed considerable anxiety over the possibility of having to terminate it should an abnormality be diagnosed. CVS clients seemed less bonded to the fetus and less concerned about losing a pregnancy several termed “replaceable.”; Thus, with its first‐trimester abortion decision, CVS redefines prenatal diagnostic issues for women.