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Cisplatin is a platinum-based chemotherapeutic agent widely used in the treatment of various solid tumors. However, a major challenge in the use of cisplatin and in the development of cisplatin derivatives, namely Pt(iv) prodrugs, is their premature reduction in the bloodstream before reaching cancer cells. To circumvent this problem, we designed liposomal nanoparticles coupled with a cholesterol-tethered amphiphilic Pt(iv) prodrug. The addition of cholesterol served to stabilize the formation of the liposome, while selectively incorporating cholesterol as the axial ligand also allowed the Pt(iv) prodrug to readily migrate into the liposomal bilayer. Notably, upon embedding into the nanoparticles, the Pt(iv) prodrug showed marked resistance against premature reduction in human plasma in vitro. Pharmacokinetic analysis in a mouse model also showed that the nanoparticles significantly extend the half-life of the Pt(iv) prodrug to 180 min, which represents a >6-fold increase compared to cisplatin. Importantly, such lipid modification did not compromise the genotoxicity of cisplatin, as the Pt(iv) prodrug induced DNA damage and apoptosis in ovarian cancer cell lines efficiently. Taken together, our strategy provides a novel insight as to how to stabilize a platinum-based compound to increase the circulation time in vivo, which is expected to enhance the efficacy of drug treatment.

Resistance to the platinum-based chemotherapy drug, cisplatin, is a significant setback in ovarian cancer. We engineered fatty acid-like Pt(IV) prodrugs that harness the fatty acid transporter CD36 to facilitate their entry to ovarian cancer cells. We show that these novel constructs effectively kill cisplatin-resistant ovarian cancer cells.

Drug resistance to the conventional platinum chemotherapy remains a major challenge for treating ovarian cancer. Herein, we present a novel approach to overcome the drug resistance by utilizing “dual-action” organometallic polymeric nanoparticles (OPNPs). The OPNPs were formed by the assembly of the organoplatinum payloads and the anionic block copolymer, methoxy polyethylene glycol-block-polyglutamic acid (MPEG5k-PGA50). The OPNPs enhance the solubility and biocompatibility of the hydrophobic organoplatinum payloads. The OPNPs enter the cancer cells via endocytosis, and the payloads loaded in the core of the nanoparticles are slowly released under the acidic conditions of endosomes. Unlike conventional platinum therapeutics, the organoplatinum compound exhibits a “dual-action” attack by triggering nuclear DNA damage and mitochondrial damage. As a result, drug-resistant ovarian cancer cells become vulnerable to the organoplatinum payloads.

We developed a spermine-conjugated lipophilic Pt(iv) prodrug that is able to reduce the cancer stem cell population in ovarian cancer. The therapeutic effect is attributed to the hydrophobic tail and cationic spermine head group, the combination of which allows the Pt(iv) prodrug to localize in mitochondria and induce corresponding damage.

This article presents a new strategy to engage coordination-driven self-assembly for platinum drug delivery. The self-assembled supramolecular hexagon is conjugated with three equivalents of Pt(IV) prodrugs and displays a superior therapeutic index compared to cisplatin against a panel of human cancer cell lines.

We present a novel design to use metal-organic cages (MOCs) to encapsulate Pt-based anticancer agents for delivery. A fluorescein-conjugated Pt(iv) prodrug of cisplatin is developed for its encapsulation in a cationic MOC via host-guest interactions, which then forms drug-loaded nanoparticles with an anionic polymer.

Introduction The purpose of this study was to quantitatively investigate the effect of magnification on fine motor skills used in endodontics. Methods This study used a novel manual dexterity test that was performed with and without magnification. An 8× operating microscope and 2.5× dental loupes were used for the magnification tests. Forty subjects, 20 with microscope experience and 20 without, participated in the study. Performance on the test was evaluated by using an accuracy scoring system, and the time needed to complete the test was recorded for each subject. Results A significant increase in accuracy score with each level of magnification was demonstrated (P ≤ .05). In addition, the use of operating microscope significantly increased the time needed to complete the test among subjects with less than 3 years of microscope experience. Conclusions The use of magnification to enhance fine motor skills was supported in all age groups and experience levels.

The management of a fistula following retrosternal esophageal reconstruction proves particularly challenging. Two distinct tissue deficits must be considered for satisfactory reconstruction. The defect in the anterior wall of the colonic replacement and that of the adjacent soft tissues of the anterior chest wall can be closed simultaneously with a single, well-planned radial forearm free flap. A patient is presented who illustrates the design and implementation of a bivalved radial forearm free flap that provides two separate epithelial surfaces.

We determined the incidence of voiding symptoms, urodynamic etiology and satisfaction with therapy in a large cohort of men with prostatism during a 12-year period.We retrospectively analyzed the records of 2,845 consecutive men who underwent urodynamic evaluation between January 1982 and December 1994. Patients were divided into groups 1 and 2 according to the years of study (between 1982 and 1988, and between 1989 and 1994, respectively). Parameters of evaluation included prevalence and distribution of voiding symptoms, urodynamic etiology of symptoms and satisfaction with therapy (medical or surgical).There was 843 evaluable patients 50 to 94 years old (mean age 63.2) Group 2 patients were younger, and had a 22% higher prevalence of nocturia and a 12% higher prevalence of daytime frequency. The prevalence of all other symptoms was the same in both groups. On urodynamics 523 patients (62%) had demonstrable evidence of bladder outlet obstruction of whom 345 (66%) had concomitant detrusor instability. Of the 843 patients 647 (77%) had detrusor instability, which was the sole diagnosis in 199 (24%). We noted low pressure/low flow in 137 patients (16%) and impaired detrusor contractility in 152 (17%), including 57 (7%) in whom the latter condition was the only diagnosis. Urodynamic findings remained the same during the entire 12-year period. Global satisfaction and symptomatic improvement were better with surgical than medical therapy, although the degree of satisfaction was independent of the urodynamic etiology of symptoms.Symptomatic men with prostatism are presenting with a greater prevalence of significant nocturia and daytime frequency than in the past with no change in urodynamic findings. In addition, patient level of satisfaction remains greater with surgical than medical therapy regardless of the urodynamic presence of bladder outlet obstruction.

In the period 1972 to 1989, 92 sports men and women were treated for stress fracture. Symptoms included localized bony pain aggravated by activity. Physical examination demonstrated point tenderness and pain on loading the bone. The majority of fractures were in the lower limbs but axial skeleton and upper limb bones were also affected. Radiographs showed evidence in only 49% of fractures. Bone scanning, on the other hand, was found to be very accurate and indicative immediately. Therefore, patients with a clinical history of stress fracture and a normal radiograph should undergo a bone scan.

Adriamycin extravasation creates a severe tissue necrosis which is unusual, because it may not appear until several weeks later, and may continue to worsen for several months. As soon as the progressive nature of the tissue necrosis is established, we recommend that an early wide excision be performed in an attempt to remove the necrotic area and the surrounding tissues containing the extravasated drugs--before it has had an opportunity to diffuse even further. Adequate debridement requires removal of any adjacent tissue that is indurated, reddened, edematous, or pale. Skin grafts take poorly if there are small amounts of Adriamycin left in the tissue of the recipient site. Synergistic effects with radiotherapy, and continued systemic Adriamycin therapy, can aggravate or recall necrosis. The administration of more dilute solutions of Adriamycin may decrease the hazard of extravasation necrosis.

Congenital lip sinuses have been reported under a large variety of terms, such as lower lip pits, lip fistulae, labial cysts, lower lip labial humps, mucous pits, mandibular processes, paramedial sinuses, accessory salivary glands, and mucous glands. They were first described by Demarquay in 1845.1

A series of 100 patients in a general plastic surgery population were interviewed by standard format to determine their retention rate of preoperative information given to them. An overall recall, or retention rate, of 35 percent was found.

The concept of automatic threshold tracking is the most recent adaptation of artificial cardiac pacemakers to physiologic needs. Earlier pacemaker innovations were primarily in the area of timing of impulse delivery, whereas more recent changes have focused on alteration of the amplitude and duration of the pacemaker stimulus. Matching of this stimulus to the cardiac excitation threshold is important because a stimulus greater than necessary is wasteful of battery energy and may produce arrhythmias, whereas a stimulus of less than threshold intensity fails to pace the heart. Because of the wide range of clinically encountered threshold levels it is impossible to design a fixed output pacer that is efficient and safe for all patients at all times. The threshold tracking pacemaker searches for and finds the threshold level, and adjusts its stimulus to just above this level. The device ensures an adequate safety margin of stimulation, but reduces the stimulus level to the lowest safe level possible. It is fully automatic, adjusts immediately to any threshold changes and is not dependent on manual alteration.

The results of this study suggest that many malignant tumors contain low levels of fibrinolytic activator activity. Evidence is presented to suggest that this low activity may be due to the presence of an inhibitor of fibrinolysis. The presence or absence of measurable fibrinolytic activator activity, and/or inhibitor in neoplastic growths may enable one to predict the probability of viable metastases to a distant site.

Entirely satisfactory treatment of complete heart block has been prevented by an inability to measure pacemaker function after implantation. Two major problems can be identified in the long-term management of pacemaker patients: first, adequate prediction of when a pacemaker will fail; and second, accurate diagnosis of the type of pacemaker failure if it occurs. Observations on dogs gave precise measurements of interelectrode impedances. A method is described of externally measuring the interelectrode resistance and capacitance of implanted pacemakers. In studies on both dogs and human beings it was found that all changes in interelectrode impedance could be identified by changes in pacemaker rate and pulse width. Serial measurements of these two parameters allowed accurate diagnosis of the different types of “pacemaker failures.” The method also enabled anticipation of failures, other than wire breakage, before they were clinically evident. We think that pacemaker performance can be adequately evaluated by this method, making unnecessary prophylactic replacement of the unit.