Integrated microsystems for controlled drug delivery

Efficient drug delivery and administration are needed to realize the full potential of molecular therapeutics. Integrated microsystems that incorporate extremely fast sensory and actuation capabilities can fulfill this need for efficient drug delivery tools. Photolithographic technologies borrowed from the semiconductor industry enable mass production of such microsystems. Rapid prototyping allows for the quick development of customized devices that would accommodate for diverse therapeutic requirements. This paper reviews the capabilities of existing microfabrication and their applications in controlled drug delivery microsystems. The next generation of drug delivery systems--fully integrated and self-regulating--would not only improve drug administration, but also revolutionize the health-care industry.     

Enlarged extraocular muscles as the presenting feature of acromegaly

: The authors report the case of a 32-year-old woman who presented with bilateral lower eyelid swelling and extraocular muscle enlargement as the initial manifestation of acromegaly. The acromegaly, however, was not diagnosed until 6 years after her symptoms began. Acromegaly should be entertained in the differential diagnosis of any patient who presents with bilateral, symmetrical extraocular muscle enlargement on computed tomographic scan, especially in the patient with normal thyroid hormone levels and no clinical findings associated with thyroid orbitopathy.     

Update in atherothrombotic disease

Crucial advances in our understanding of the pathogenesis of atherothrombosis, defined as atherosclerosis and its thrombotic complications, have been achieved during the past two decades. The historical hypothesis of pathogenesis ("lipid accumulation") has evolved to integrate several factors contributing to the initiation and evolution of this complex disease. Endothelial dysfunction is considered to be the earliest event in atherogenesis. Inflammation and apoptosis play critical roles in its progression and onset. Tissue factor is postulated to be a central actor in determining plaque thrombogenicity. A hyperreactive state of the blood ("vulnerable blood") may be responsible for one-third of all the acute coronary syndromes. This review will discuss emerging concepts in the pathogenesis of and therapeutic approaches to atherothrombotic disease.     

In-stent recurrent stenosis after carotid artery stenting: life table analysis and clinical relevance

OBJECTIVES: Carotid artery stenting has been proposed as an alternative to carotid endarterectomy in cerebral revascularization. Although early results from several centers have been encouraging, concerns remain regarding long-term durability of carotid artery stenting. We report the incidence, characteristics, and management of in-stent recurrent stenosis after long-term follow-up of carotid artery stenting. METHODS: Carotid artery stenting (n = 122) was performed in 118 patients between September 1996 and March 2003. Indications included recurrent stenosis after previous carotid endarterectomy (66%), primary lesions in patients at high-risk (29%), and previous ipsilateral cervical radiation therapy (5%). Fifty-five percent of patients had asymptomatic stenosis; 45% had symptomatic lesions. Each patient was followed up with serial duplex ultrasound scanning. Selective angiography and repeat intervention were performed when duplex ultrasound scans demonstrated 80% or greater in-stent recurrent stenosis. Data were prospectively recorded, and were statistically analyzed with the Kaplan-Meier method and log-rank test. RESULTS: Carotid artery stenting was performed successfully in all cases, with the WallStent or Acculink carotid stent. Thirty-day stroke and death rate was 3.3%, attributable to retinal infarction (n = 1), hemispheric stroke (n = 1), and death (n = 2). Over follow-up of 1 to 74 months (mean, 18.8 months), 22 patients had in-stent recurrent stenosis (40%-59%, n = 11; 60%-79%, n = 6; > or =80%, n = 5), which occurred within 18 months of carotid artery stenting in 13 patients (60%). None of the patients with in-stent recurrent stenosis exhibited neurologic symptoms. Life table analysis and Kaplan-Meier curves predicted cumulative in-stent recurrent stenosis 80% or greater in 6.4% of patients at 60 months. Three of five in-stent recurrent stenoses occurred within 15 months of carotid artery stenting, and one each occurred at 20 and 47 months, respectively. Repeat angioplasty was performed once in 3 patients and three times in 1 patient, and repeat stenting in 1 patient, without complications. One of these patients demonstrated asymptomatic internal carotid artery occlusion 1 year after repeat intervention. CONCLUSIONS: Carotid artery stenting can be performed with a low incidence of periprocedural complications. The cumulative incidence of clinically significant in-stent recurrent stenosis (> or =80%) over 5 years is low (6.4%). In-stent restenosis was not associated with neurologic symptoms in the 5 patients noted in this cohort. Most instances of in-stent recurrent stenosis occur early after carotid artery stenting, and can be managed successfully with endovascular techniques.     

Nuclear hormone receptor co-regulators

The critical role of nuclear hormone receptor co-activators in gene expression has been extensively studied for the past few years. Co-regulators (co-activators and co-repressors) are known to utilize various enzymatic activities, in addition to molecular interactions, to modulate gene expression in response to hormonal signals. Recent studies that demonstrate the role of co-regulators in cancer and developmental disorders have revealed their possible role as targets of therapy. A greater understanding of the cellular physiology of co-regulators is necessary to explore the pathological ramifications of hormone-dependent diseases, and to discover new treatments.     

Priapism--a review of the medical management

Priapism is characterised by the presence of prolonged, often painful penile erection in the absence of a sexual stimulus. This rare condition has a range of aetiologies, but is most common following self-administration of injection therapy for impotence. Priapism may be classified into high- and low-flow states. Low-flow priapism is an emergency ischaemic condition requiring prompt recognition and treatment to avoid devastating long-term complications of erectile dysfunction. Wide-ranging medical therapies are covered in this review. Diagnostic and treatment algorithms are suggested in light of the current available literature.     

Quality of life in patients with pituitary tumors: a preliminary study

Patients with pituitary tumors frequently complain of quality of life problems despite normal hormonal blood levels. The goals of the study were to determine whether the sickness-related quality of life reported by these patients was poorer than that expected by the general population and whether some of these complaints and areas of dysfunction were more troublesome than others. Forty-three patients from a southeast Michigan pituitary disorders support group volunteered to complete a survey focusing on demographic, disease data and common complaints plus the Sickness Impact Profile (SIP). The results indicated that mental and physical fatigue were the most troublesome symptoms with sleep and libidinal complaints also of significant concern. The SIP indicated significant discontent among patients with regard to overall quality of life. Although this observational investigation seemed to underscore the fact that patients with pituitary tumors have a decreased quality of life despite apparently normal hormonal status, further subgroup analysis and subsequent surveys will be required to determine the actual significance of these findings.     

HIV/AIDS risk behaviors and correlates of injection drug use among drug users in Pakistan

We studied prevalence and correlates of injection drug use, awareness of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), and risky behaviors among drug users serviced by a nongovernmental organization catering to drug users in three Pakistani cities (Quetta, Peshawar, and Rawalpindi). Logistic regression analysis was used to identify correlates of injection drug use. Of 608 drug users, 99.8% were male; median age was 32 years, and 44% were married. Most (79.8%) were Pakistani; 15.3% were Afghani. The majority used heroin (98.7%), mostly by inhalation; 15.2% injected drugs. Only 41% had heard of HIV/AIDS, and 30% had been paid for donating blood. Injection drug use and needle sharing were highest in Quetta. Injecting drug users (IDUs) were nearly twice as likely to have donated blood and to have heard about HIV/AIDS compared to other drug users. Interventions to discourage transitions to injection, increase HIV testing, and safeguard the blood supply in Pakistan are urgently needed.     

Doege-Potter syndrome: hypoglycemia associated with malignant solitary fibrous tumor

We report a case of recurrent solitary fibrous tumor with associated hypoglycemia, the "Doege-Potter syndrome." These are rare tumors with a 12-13% rate of malignancy. The syndrome of hypoglycemia is seen in less than 5% of the cases, and the associated tumors are large with a high mitotic rate. The cause of hypoglycemia is related to insulin-like growth factors produced by these tumors. Resection in many cases is curable with resolution of the hypoglycemia. We discuss the different signs and symptoms and literature evidence of treatment options and follow-up.     

Endothelium and hypertensive disorders in pregnancy

Pregnancy-induced hypertension is one of the complications that obstetricians fear most due to its sudden appearance, its changing clinical presentation, its rapid evolution, and its association with high fetal and maternal morbidity and mortality. Because of these reasons, preeclampsia has been studied widely. But although the search for answers to many questions about its etiopathogenesis and physiopathology has led to numerous researches, after many years of studies and efforts there still exist obscure and enigmatic aspects about them. Today, various risk factors for the development of this entity have been identified, and a combination of different hypotheses has been proposed to try to find an approximation to the real solution for this problem, which could probably lead to better therapeutic management.