Spontaneous Reversal of P‐Glycoprotein Expression in Multidrug Resistant Cell Lines*

Abstract: Increased expression of P‐glycoprotein encoded by the mdr‐1 gene is a well‐characterised mechanism for resistance to cancer chemotherapeutic drugs in cell lines. However, the P‐glycoprotein expression after removal of the selection pressure has not fully been elucidated. The stability of P‐glycoprotein expression in the presence (+) and absence (?) of vincristine (30 or 150 nM) was studied in multidrug resistant K562 cell lines (VCR30+, VCR150+, VCR30? and VCR150?) for 11 months. The P‐glycoprotein protein and mdr‐1 mRNA levels were determined at regular intervals using flow cytometry and real‐time PCR, respectively. Chemosensitivity to a panel of antineoplastic drugs was measured using an MTT assay. The presence of vincristine (VCR30+ and VCR150+) resulted in high and stable levels of P‐glycoprotein and mdr‐1 mRNA during the whole period compared to wild type. As for the VCR30? and VCR150? subcultures, the expressions of P‐glycoprotein and mdr‐1 mRNA were stable for five months, and then the levels decreased rapidly. Concomitantly, the sensitivity to drugs known as P‐glycoprotein substrates was restored. In conclusion, resistant cells growing in the presence of the inducing drug have a stable P‐glycoprotein expression and resistance level, but removing the inducing drug may result in a sudden and rapid lowering of P‐glycoprotein and mdr‐1 mRNA levels as long as five months after drug withdrawal.     

APPLICATION OF PROGNOSTIC SCORING SYSTEMS IN DIFFERENTIATED THYROID CARCINOMA

Background : Total thyroidectomy is widely practised in Australasia for papillary and follicular thyroid carcinoma. Data from large overseas series have demonstrated that patients with these cancers may be separated into risk groups based on clinicopathological prognostic factors. Furthermore, evidence suggests that low-risk patients may be safely treated with less than total thyroidectomy. The aim of the present paper was to determine what proportion of our patients with papillary and follicular thyroid cancer were in the low-risk group in order to select candidates for less aggressive treatment. Methods : A prospectively documented series of 175 previously untreated patients with papillary and follicular thyroid carcinoma, treated principally by total thyroidectomy over a 10-year period, was divided into risk groups using the Mayo Clinic, Lahey Clinic and Memorial Hospital prognostic scoring systems. Complication rates for 103 patients treated by total thyroidectomy were also studied and reported. Results : Women outnumbered men by 2.3:1. There were 128 papillary carcinomas (73%) and 47 follicular cancers (27%). These tumours were < 4 cm in diameter in 81% of patients, and 41% of patients were 40 years of age or younger. Low-risk patients accounted for 75, 81 and 45% of the study group, respectively, when the three prognostic scoring systems were applied to our patient population. The rates for recurrent laryngeal nerve palsy and permanent hypoparathyroidism for patients having total thyroidectomy were 1 and 1.9%, respectively. In the low-risk group there were no permanent complications. Conclusion : Most patients treated at Royal Prince Alfred Hospital during the past 10 years were low-risk patients who may have been eligible for less aggressive surgical treatment.     

Tele-counseling based on motivational interviewing to change sexual behavior of women living with HIV: a randomized controlled clinical trial

AIDS and Behavior - Sexual transmission accounts for the majority of new HIV infections in Iran. More than 80% of HIV-positive persons are sexually active, and nearly 68% reported never using a...     

Successful Management of Plastic Bronchitis in a Child Post Fontan: Case Report and Literature Review

Purpose

Plastic bronchitis is the occlusion of the major bronchial airways by a firm, gelatinous mucoid cast. It is a rare condition, which while classically described in asthma and sickle cell disease has greater mortality in patients with congenital heart disease. The management of this disease is obscure given the lack of clinical data regarding treatment therapies.

Methods

We describe a case of an 11-year-old female status after Fontan surgery who presented with respiratory distress secondary to atelectasis of the right lung.

Results

A bronchoscopy was performed demonstrating an obstructing bronchial cast with successful extraction. The plastic bronchitis continued to recur and she was placed on multiple inhaled mucolytics as well as inhaled tissue plasminogen activator with temporary resolution. Further evaluation of the etiology of her casts revealed that she had elevated pulmonary arterial pressures. Repeated bronchoscopic removal of the casts was utilized as well as continuation of the aggressive airway clearance. Ultimately fenestration of her Fontan was performed along with treatment of pulmonary vasodilators sildenafil and bosentan. Although there was improvement of the cast formation, her airway clearance could only be weaned to four times a day therapy with which she was discharged home after a 3-month hospitalization. She continues to remain on this therapy and has not required hospitalization since the initial incident over 1?year ago.

Conclusions

Plastic bronchitis in a patient with Fontan physiology presents a treatment dilemma that may require comprehensive therapy in severe cases such as described.     

The application of tissue-engineered preputial matrix and fibrin sealant for urethral reconstruction in rabbit model

Background

To introduce the role of fibrin sealant and preputial acellular matrix (PAM) as a new source of inert collagen matrix for urethral reconstruction.

Methods

A ventral urethral segmental defect was created in 24 male rabbits divided into four groups. In group 1 (G1), urethrotomy was closed in layers. In group 2 (G2), closure was followed by applying fibrin sealant. In groups 3 (G3) and 4 (G4), urethroplasty was performed with a patch graft of PAM, and in G4, fibrin sealant was also applied. Serial urethrography was performed before and after the operation. Then, the animals were euthanized, and their urethra was excised 1, 3, and 9 months postoperatively for further electron microscopic examination, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) technique, and immunohistochemical (IHC) staining with CD34, CD31, desmin, SMA, and α-actin.

Results

In G1 and G2, the fistula repair failed in all the time points. In G3 and G4, serial urethrography confirmed the maintenance of a wide urethral caliber without signs of strictures or extravasations. Satisfactory vascularity was observed in G3 and G4 during the whole study, which was more significant in G4 after 9 months of follow-up. The presence of a complete transitional cell layer was confirmed over the graft in G3 and G4 in all time points. IHC staining confirmed the effectiveness of fistula repair in G3 and G4, 3 months postoperatively.

Conclusion

This rabbit model showed that PAM combined with fibrin sealant may herald a reliable option for repairing segmental urethral defects.     

ACS national surgical quality improvement program: Targeting quality improvement in Canadian pediatric surgery

Purpose

The pediatric NSQIP program is in the early stages of facilitated surgical quality improvement for children. The objective of this study is to describe the initial experience of the first Canadian Children’s Hospital participant in this program.

Method

Randomly sampled surgical cases from the “included” case list were abstracted into the ACS-NSQIP database. These surgical procedure-specific data incorporate patient risk factors, intraoperative details, and 30 day outcomes to generate annual reports which provide hierarchical ranking of participant hospitals according to their risk-adjusted outcomes.

Results

Our first risk-adjusted report identified local improvement opportunities based on our rates of surgical site infection (SSI) and urinary tract infection (UTI). We developed and implemented an engagement strategy for our stakeholders, performed literature reviews to identify practice variation, and conducted case control studies to understand local risk factors for our SSI/UTI occurrences. We have begun quality improvement activities targeting reduction in rates of SSI and UTI with our general surgery division and ward nurses, respectively.

Conclusions

The NSQIP pediatric program provides high quality outcome data that can be used in support of quality improvement. This process requires multidisciplinary teamwork, systematic stakeholder engagement, clinical research methods and process improvement through engagement and culture change.     

Venous thromboembolism after Diaphragm Pacing in amyotrophic lateral sclerosis

Introduction: Patients with amyotrophic lateral sclerosis (ALS) are prone to venous thromboembolism (VTE) and secondary complications. Because there is an increased incidence of VTE after surgical procedures, placement of a Diaphragm Pacing System (DPS) in ALS patients as treatment for respiratory muscle weakness could potentially increase the incidence of VTE, especially in patients with limited mobility. Methods: We implanted a DPS in 10 ALS patients who met the criteria for this procedure. They underwent a preoperative evaluation as recommended by the guidelines. Results: We report 2 patients with no symptoms of deep vein thrombosis (DVT) before the surgical procedure who then developed perioperative VTE. Conclusions: These patients highlight the need to consider preoperative screening for DVT and postoperative thromboprophylaxis in high‐risk ALS patients who undergo DPS placement. Muscle Nerve 50 : 863–865, 2014