Glatiramer acetate in the treatment of multiple sclerosis

Glatiramer acetate is an immunomodulating drug used in the treatment of multiple sclerosis. It consists of a copolymer of amino acid residues in the same stoichiometric proportions as in myelin basic protein. Its mechanism of action is not entirely known and is probably multifaceted, with deletion of some immune cell populations and stimulation of others in these patients. Some mechanisms involve neuroprotectant effects. There is ample evidence of its efficacy in relapsing-remitting disease, using both clinical and imaging measures of disease activity, and in this paper we review the clinical and basic studies of this drug. Finally we discuss how some of its neuroprotectant effects may be useful in neurodegeneration such as is seen in more advanced cases of multiple sclerosis and other diseases such as amyotrophic lateral sclerosis and Parkinson’s disease.     

Thyroid disease and pregnancy: degrees of knowledge.

OBJECTIVE: The literature on the impact of thyroid abnormalities on pregnancy and the postpartum has expanded rapidly over the last two decades. The objective of the present study was to determine the level of knowledge of endocrinologists, obstetrician/gynecologists, internists, and family physicians in regard to thyroid disease and pregnancy. DESIGN: A 16-item questionnaire on issues related to thyroid disease and pregnancy was developed. Endocrinologists (n = 116), obstetrician/gynecologists (n = 81), internists (n = 109), and family physicians (n = 99) were asked to complete the questionnaire. Physician self-report of confidence regarding degree of knowledge was obtained through completion of a seven-point Likert scale. MAIN OUTCOME: The percentage of questions answered correctly by all physicians was 63%. Endocrinologists had the highest correct response rate (77%), followed by obstetrician/gynecologists. Hierarchical regression analysis revealed that medical specialty, years of training, confidence level, and whether or not the physician treated pregnant women were significantly related to the overall score. CONCLUSIONS: The present study demonstrates a suboptimal level of knowledge regarding thyroid disease and pregnancy among physicians in four specialties. A comprehensive physician education program is needed.     

Incorporation of protein-eluting microspheres into biodegradable nerve guidance channels for controlled release.

Nerve guidance channels (NGCs) promote axonal regeneration after transection injury of the peripheral nerve or spinal cord, yet this regeneration is limited. To enhance regeneration further, we hypothesize that localized delivery of therapeutic molecules combined with the NGC is required. In an attempt to achieve such an NGC, we designed and synthesized a novel NGC in which protein-encapsulated microspheres were stably incorporated into the tube wall. Specifically, poly(lactide-co-glycolide) (PLGA 50/50) microspheres were physically entrapped in the annulus between two concentric tubes, consisting of a chitosan inner tube and a chitin outer tube. Taking advantage of the extensive shrinking that the outer chitin tube undergoes with drying, >15 mg of microspheres were loaded within the tube walls. Using BSA-encapsulated microspheres as the model drug delivery system, BSA was released from microsphere loaded tubes (MLTs) for 84 days, and from freely suspended PLGA microspheres for 70 days. An initial burst release was observed for both MLTs and free microspheres, followed by a degradation-controlled release profile that resulted in a higher release rate from MLTs initially, which was then attenuated likely due to the buffering effect of chitin and chitosan tubes. Epidermal growth factor (EGF), co-encapsulated with BSA in PLGA 50/50 microspheres in MLTs, was released for 56 days with a similar profile to that of BSA. Released EGF was found to be bioactive for at least 14 days as assessed by a neurosphere forming bioassay.     

Human papillomavirus and HIV coinfection and the risk of neoplasias of the lower genital tract: a review of recent developments

ONE OF THE RISK FACTORS FOR HUMAN PAPILLOMAVIRUS (HPV) INFECTION and subsequent lower genital tract neoplasias and cancers is impaired cell-mediated immunity. HIV-positive women with severe immunosuppression are 5 times more likely than HIV-negative women to have lower genital tract neoplasias. A corresponding increase in the risk of invasive vulvar and anal cancers, but not of cervical cancer, has also been observed among HIV-positive women. Treatment failure and recurrence of neoplasia occur much more frequently among HIV-positive than among HIV-negative women. In this review, we discuss recent advances in the understanding of the relation between HIV and HPV coinfection and the development of lower genital tract neoplasias and cancers in women. In addition, we present strategies for monitoring and treating noninvasive and invasive neoplasias of the lower genital tract in HIV-positive women.     

The Distally Based Sural Artery Flap for Ankle and Foot Coverage

The sural artery flap is a distally based fasciocutaneous flap that has many advantages to offer for coverage in the foot and ankle area. It has the largest arc of rotation of all the regional flaps and does not require sacrifice of any major artery, and moderate-to-large-sized defects can be covered adequately. The dissection technique is simple, and donor site morbidity is minimal. We report our experience with 17 cases. Age range was from 13 to 56 years. Ten (59%) defects were posttraumatic, 3 (17%) were related to reconstructive surgery of the foot or tendon Achilles', 2 (11%) resulted from tumor resection, and 1 each were from infection and gunshot wound. The smallest flap was 6 x 4 cm and the largest was 15 x 12 cm, with the average size being 11 x 7.5 cm. In 5 cases, the donor site was closed primarily, and in other cases, split-thickness skin graft was needed. The short saphenous vein was included in the pedicle in all cases. There was no incidence of complete flap necrosis. Follow-up ranged from 3 to 30 months. Two cases (12%) developed partial superficial necrosis. In 1 case, there was partial wound dehiscence that needed debridement and repair. Another case had postoperative discharge, which subsided after removal of the calcaneal plate. None of the patients complained of any functional problem related to loss of sensation along the lateral border of the foot. The sural island flap is a reliable, safe, and easy method of providing soft tissue coverage in the area of the foot and ankle.     

Delivering syringe exchange services through “satellite exchangers”: the Sacramento Area Needle Exchange, USA

An important operational aspect of Syringe Exchange Programmes (SEPs) is the venue of service delivery. This report describes the programmatic features of the Sacramento Area Needle Exchange (SANE), an illegal SEP operating in California, USA. SANE utilises “satellite exchangers” to distribute the bulk of its syringes and HIV risk reduction supplies. Advantages of relying primarily on Designated Exchangers (DE) for delivery of SEP services are that it: (1) allows for coverage of a large geographical area; (2) keeps operational cost low; (3) provides syringes to clients who may not want to or cannot use fixed site programmes; (4) limits the possibility of detection of programme personnel and clients by law enforcement. Limitations are that: (1) it is not as conducive as fixed sites to providing a wide range of ancillary services; (2) it may not be optimal for drug users who do not want to be reliant on other people for access to syringes; (3) those who receive services from a satellite exchanger may not derive as much counselling and referral services as direct exchangers. The lack of legal status, political support and adequate funding threatens the programme’s existence.