Electron microscopy for inorganic-type drug delivery nanocarriers for antitumoral applications: what does it reveal?

The use of nanoparticles with the ability to transport drugs in a selective and controllable manner directly to diseased tissues and cells has improved the therapeutic arsenal for addressing unmet clinical situations. In recent years, a vast number of nanocarriers with inorganic, organic, hybrid and even biological nature have been developed especially for their application in the oncology field. The exponential growth in the field of nanomedicine would not have been possible without the also-rapid expansion of electron microscopy techniques, which allow a more precise observation of nanometric objects. The use of these techniques provides a better understanding of the key parameters which rule the nanoparticles' synthesis and behavior. In this review, the recent advances made in the application of inorganic nanoparticles to clinical uses and the role which electron microscopy has played are presented.

Successful management of severe gastroesophageal reflux disease with laparoscopic Nissen fundoplication.

BACKGROUND: Nissen fundoplication has been shown to be superior to medical treatment in the management of severe or complicated gastroesophageal reflux disease (GERD). Rapid advances in minimally invasive surgical technique and recognition of the advantages of reduced incision-related morbidity have fostered application of laparoscopic techniques to antireflux surgery. A prospective evaluation of 70 patients undergoing laparoscopic Nissen fundoplication for severe GERD was undertaken. PATIENTS AND METHODS: Rigid selection criteria for laparoscopic Nissen fundoplication included severe or refractory disease with documentation of abnormal esophageal acid exposure by 24-hour pH probe monitoring, documentation of a mechanically defective lower esophageal sphincter by esophageal manometry, and absence of severe esophageal and/or gastric motility disorders. RESULTS: Sixty-eight of 70 patients were completed laparoscopically with an intraoperative morbidity rate of 9%. Major postoperative complications occurred in 3 patients (4%) and included deep venous thrombosis (n = 1), delayed gastric leak (n = 1), and trocar site hernia (n = 1). The average hospital stay was 3.0 days, and the average time to return to normal activity was 7.0 days. All patients experienced relief of symptoms of reflux with mean follow-up of 7.7 months. Transient, mild dysphagia was experienced by 37% of patients, and persistent, severe dysphagia by 7%. The mean increase in lower esophageal sphincter pressure was 16.2 mm Hg. The total and intra-abdominal sphincter lengths increased an average of 1.5 and 1.4 cm, respectively. CONCLUSIONS: These preliminary data suggest that laparoscopic Nissen fundoplication can be performed by experienced laparoscopic surgeons with excellent symptomatic and physiologic results and a morbidity rate comparable to conventional open antireflux procedures. Rigid patient selection criteria will help identify the patients most likely to benefit from reconstruction of a mechanically defective lower esophageal sphincter. Adherence to established operative principles for Nissen fundoplication will reduce the incidence of significant postfundoplication symptoms.

Efficacy of slow-release oral isradipine in moderate-to-severe hypertension with add-on spirapril.

The new slow-release oral formulation (SRO) of isradipine, a dihydropyridine calcium antagonist, was evaluated in 57 patients who had moderate-to-severe hypertension following a 2-week wash-out period and a 2-week placebo period. The angiotensin-converting enzyme (ACE) inhibitor spirapril, at a dose of 6 mg/day, was added to the treatment of those not responding to 5 mg/day isradipine SRO alone. After 4 weeks of active treatment, isradipine alone normalized blood pressure (diastolic blood pressure < or = 90 mm Hg) in 38 (66.6%) patients whereas a further 4 weeks of treatment with the combination of isradipine and spirapril led to normalization in 14 of the 19 (73.7%) patients with partial or nil blood pressure responses. Side-effects were mild and transient and were observed in nine patients (15.8%). Isradipine SRO is an effective and well-tolerated antihypertensive agent and combination with spirapril appears to enhance its efficacy without an increase in side-effects.

Isradipine dose-confirmation study in Filipino patients with mild to moderate hypertension.

The effective and well tolerated dose of isradipine was determined in 130 Filipino patients with mild to moderate essential hypertension in a multicentre study with a 2-week placebo pretreatment period followed by an 8-week active treatment period. 37 male and 93 female patients (mean age 51 years, mean weight 59.9kg) participated in the study. Average systolic/diastolic blood pressure on admission was 163.8/103.7mm Hg. Results showed isradipine normalised sitting diastolic blood pressures in 109 of 130 (83.8%) patients. 71 patients (54.6%) were receiving isradipine 1.25mg twice daily while 38 patients (29.2%) required a dose of 2.5mg twice daily. A drop of greater than or equal to 10mm Hg in sitting diastolic blood pressure was achieved in 71 patients (54.6%) administered isradipine 1.25mg twice daily and 44 patients (33.8%) on isradipine 2.5mg twice daily. Heart rate was not significantly changed with either dosage. Drug-related adverse effects were only transient in duration and mild to moderate in severity. No patient discontinued treatment because of these effects. This study provides confirmatory evidence of the clinical efficacy and tolerability of a daily dose of less than or equal to 5mg isradipine in Filipino patients with mild to moderate hypertension.