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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.

A long-standing challenge in the treatment of ovarian cancer is drug resistance to standard platinum-based chemotherapy. Recently, increasing attentions hasve been drawn to the use of self-assembled metal-organic complexes as novel therapeutics for cancer treatment. However, high hydrophobicity that is often associated with these structures lowers their solubility and hinders their clinical translation. In this article, we present a proof-of-concept study of using nanoprecipitation to formulate the hydrophobic metal-organic cages and facilitate their use in treating chemoresistant ovarian cancer. The Pt6L4 Cage 1 is an octahedral cage formed by self-assembly of six 1,10-phenanthroline-Pt(II) centers and four 2,4,6-tris(4-pyridyl)-1,3,5-triazine ligands (L). Cage 1 is able to trigger DNA damage and exhibits promising in vitro potency against a panel of human ovarian cancer cell lines. However, due to the large portion of aromatic components, this cage structure has very limited solubility in cell culture media (

This case report highlights the present threat and challenges with treatment and transmission of infections caused by carbepenem-resistant enterobacteriaceae (CRE) within in-patient spinal rehabilitation units. The setting is within the Spinal Cord Injury Unit, Royal North Shore Hospital, Sydney, Australia. We report the case of a 45-year-old female with T9 complete paraplegia who developed CRE urinary tract infection (UTI) and sepsis 1 month post injury while in an in-patient spinal rehabilitation unit. We describe the challenges in treatment with colistin, the implications of infection on her rehabilitation and challenges in containing the spread of CRE to other patients in the unit. We present our experience with the management of CRE bactaeraemia in a spinal rehabilitation unit and the enhanced importance of infection control and surveillance strategies required to successfully contain risk of transmission.

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.

Hemangiopericytoma (HPC) is an uncommon tumor which was first described in 1942. There are no unique radiological or clinical identifiers that can reliably aid in preoperative diagnosis. Surgery is the only reliable therapy as both chemotherapy and radiotherapy have proven ineffective in several series. The outcome is difficult to predict; the only reliable predictor is the presence or absence of metastasis. We report on a 63-year-old female with a large left renal HPC.

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.

The clinical features of melanoma and various regimens of treatment have been studied throughout the years. A melanoma can be cured if it is discovered early and adequately removed surgically. Survival decreases progressively as tumors recur locally, satellite nodules develop, and regional lymph nodes become involved.

Intraoral minor salivary gland carcinomas are relatively uncommon. The glands are concentrated in the mucosa of the mouth but occur over a wide area in the head and neck region. Little is known about the etiologic factors responsible for these tumors. Histologically, most salivary gland tumors are similar to those occurring in the parotid gland, but are more likely to be malignant. The most common presentations is an asymptomatic submucosal mass on the palate in a patient in the fifth or sixth decade, although it can occur in any age group. Neck node metastases occur in about one fourth of these patients. Surgical resection is the treatment of choice; irradiation may be a useful adjunctive method of palliation. Multiple recurrences over a long period of time are the rule, with 5 year survival for all malignant lesions being 44.5 per cent. The survival decreases another 10 per cent for each succeeding 5-year period of follow-up.

A new technique consisting of the subcutaneous insertion of molded Silastic implants in patients with pectus excavatum deformities is presented. This method of correction should be considered for patients who are devoid of cardiac and respiratory symptoms and for those in whom the only operative indication is cosmetic. The surgical technique is simple, the complication rate is low, and patient tolerance is good. The cosmetic appearance at one year appears excellent.

This report concerns a Negro infant with interruption of the aortic arch and complete transposition of the great vessels. The presenting features were congestive heart failure and differential cyanosis. The marked cyanosis of the hands was in sharp contrast to the relatively normal color of the feet. The diagnosis was established during life by detailed hemodynamic and angiocardiographic studies. These are correlated with the salient clinical features of this case and with similar cases reported in the literature.

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.

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.