Role of p27Kip1 and Cyclin-Dependent Kinase 2 in the Proliferation of Non-Small Cell Lung Cancer

The cell cycle is governed by a family of cyclin-dependent kinases (Cdks). Cdk2 forms a functional complex with cyclin E and plays a pivotal role in the regulation of G1/S transition. Cdk2 activity is negatively regulated by interactions with inhibitors. p27^Kip1, one of the most potent inhibitors of Cdk2, was recently identified as a powerful negative prognostic marker in non-small cell lung cancer as well as in colorectal and breast cancer. In the present study, the expression of p27 and Ki-67 antigen in nonneoplastic and cancerous lung tissues was determined by immunohistochemistry. After establishing that the antibody-measured p27 labeling index was a good reflection of the level of p27 expression measured by Western blotting, we show that p27 labeling index is decreased in cancerous lung tissues, compared with nonneoplastic lung tissues, and exhibits a significant inverse relation to the proliferation marker Ki-67 antigen, detected with monoclonal antibody MIB-1. Consistent with these data, all cancerous lung tissues showed enhanced degradation activity of p27 compared with nonneoplastic lung tissues and, in addition, increased levels of the phosphorylated form of Cdk2, as determined with Western blot analysis. The H1 histone kinase activity associated with Cdk2 was also increased in non-small cell lung cancers. Statistical analysis showed that proliferative activity as measured by MIB-1 labeling index was highly correlated with Cdk2 activity (r = 0.767, P < 0.0015). These results suggest that p27 and Cdk2 may play an important role in the proliferation of non-small cell cancer.     

An accessory mitral valve leaflet causing left ventricular outflow tract obstruction and associated with severe aortic incompetence

This case report describes a 20-year-old woman with Turner's syndrome who presented with reduced effort tolerance limited by dyspnea. She had previously been on pediatric cardiology follow-up for congenital subvalvular aortic stenosis first diagnosed at age 7. Unfortunately she defaulted after two visits before any intervention could be done. Transthoracic echocardiography demonstrated severe aortic incompetence (AI) with a membrane-like structure in the left ventricular outflow tract (LVOT). The mean pressure gradient across the LVOT on continuous wave Doppler was 41 mmHg. The membranous interventricular septum appeared aneurysmal and it was observed that the "subaortic membrane" had a connection to the anterolateral papillary muscle via a strand of chordal tissue. Further images were captured using two-dimensional and three-dimensional transthoracic and transesophageal echocardiography (iE33, Philips Medical Systems, Andover, MA, USA). After a review of the literature it was concluded that this appeared to be an accessory mitral valve (AMV) leaflet causing LVOT obstruction associated with AI. AMV tissue is a rare congenital malformation causing LVOT obstruction. Because it is so unusual, it may not be immediately recognizable even in a high volume echocardiography laboratory. The clue which helped with the diagnosis was the strand of chordal tissue which connected the mass to the papillary muscle. This anomaly is often associated with LVOT obstruction.     

Azelnidipine and amlodipine: a comparison of their pharmacokinetics and effects on ambulatory blood pressure.

We objected: 1) To compare the effects of azelnidipine and amlodipine on 24-h blood pressure; 2) To monitor the plasma concentration vs. the time profile in order to assess the association between pharmacokinetics and hypotensive activity after administration of either drug for 6 weeks. Blood pressure and pulse rate were measured by 24-h monitoring with a portable automatic monitor in a randomized double-blind study of 46 patients with essential hypertension. Azelnidipine 16 mg (23 patients) or amlodipine 5 mg (23 patients) was administered once daily for 6 weeks. Pharmacokinetics were analyzed after the last dose was taken. Both drugs showed similar effects on the office blood pressure and pulse rate. During 24-h monitoring, both drugs caused a decrease in systolic blood pressure of 13 mmHg and had a similar hypotensive profile during the daytime period (07:00-21:30). The pulse rate decreased by 2 beats/min in the azelnidipine group, whereas it significantly increased by 4 beats/min in the amlodipine group. Similar trends in the blood pressure and pulse rate were observed during the nighttime (22:00-6:30) and over 24 h. Excessive blood pressure reduction during the nighttime was not seen in either group. The pharmacokinetic results indicated that the plasma half-life (t1/2) of amlodipine was 38.5 +/- 19.8 h and that of azelnidipine was 8.68 +/- 1.33 h. Despite this difference in pharmacokinetics, the hypotensive effects of amlodipine and azelnidipine were similar throughout the 24-h administration period.     

Factors related to urinary incontinence among the Malaysian elderly

Background

Urinary incontinence is a prevalent condition in the elderly that is the spontaneous leakage of urine. It is an age-related problem and increases especially in people aged above 65 years. It can cause many psychological, behavioral, biological, economic and social effects. The treatment of urinary incontinence can reduce morbidity and mortality. Thus, this study aimed to determine the effects of variables including age, ethnicity, gender, education, marital status, body weight, blood elements and nutritional parameters on urinary incontinence among the Malaysian elderly.

Methods

The study was on 2322 non-institutionalized Malaysian elderly. The hierarchy logistic regression analysis was applied to estimate the risk of independent variables for urinary incontinence among respondents.

Results

The findings indicated that approximately 3.80% of subjects had urinary incontinence. In addition, constipation was found a significant factor that increased the risk of urinary incontinence in samples (p=0.006; OR=3.77). The increase in dietary monounsaturated fat (p=0.038; OR=0.59) and plasma triglyceride levels (p=0.029; OR=0.56) significantly reduced the risk of incontinence in subjects. Many of suspected variables including socio-demographic factors, diseases, nutritional minerals, blood components and body weight were non-relevant factors to urinary incontinence in respondents.

Conclusions

Constipation increased the risk of urinary incontinence in subjects, and increase in dietary monounsaturated fat and plasma triglyceride levels decreased the risk.

     

Reproductive factors influencing bone mineral density in postmenopausal women

This study examined the relationship between reproductive characteristics and bone mineral density (BMD) in postmenopausal women who had been referred to the menopause clinics of the National Population and Family Development Board and of the Hospital Kuala Lumpur from July 2011 to January 2012. The participants of this study were 201 postmenopausal Malaysian women aged 45–71 years. Some socio-demographic, lifestyle, and reproductive factors were recorded. Calcaneal BMD was measured by quantitative ultra-sonography. Correlations of reproductive factors with BMD were assessed by Pearson’s correlation test and multiple regression analysis. Age at menopause was not significantly correlated with BMD, while the years after menopause, age at the first menstrual period, number of pregnancies, and total lactation periods were inversely correlated with it. Among reproductive factors, only the association between lactation duration and BMD remained significant after adjusting for age, body mass index, activity, and calcium intake. The results indicated that except for prolonged total time of lactation, other reproductive factors were not significantly associated with BMD in postmenopausal women.     

Unmet needs among disabled elderly Malaysians

Unmet need as a significant factor affecting quality of life in later life has recently received considerable attention in gerontological research. The main aim of this study was to identify the prevalence, predicting factors, and negative consequence of unmet need among older Malaysians. The findings may be useful to reduce unmet need and the burden of its adverse consequence. The sample for this study consists of 400 functionally disabled elderly people aged 60 and over was obtained from a large national survey. Unmet need was operationally defined based on Manton's (1989) criteria. The findings from the present study showed about 18.0% of functionally disabled older Malaysians suffer from unmet need. Logistic regression revealed that gender (being male) and chronic health conditions are statistically associated with increased odds of unmet need after adjusting for other possible risk factors. Further results indicated that unmet need statistically increases odds of fall as a negative consequence of unmet need. The high prevalence rates of unmet need among disabled elderly men and chronically ill older persons suggest that policy makers should pay more attention to this vulnerable group to achieve good quality of life. The implications and limitations of the present study are discussed.     

Factors Affecting Tumor Ablation during High Intensity Focused Ultrasound Treatment

Background/Aims

High intensity focused ultrasound (HIFU) utilizes a targeted extracorporeal focused ultrasound beam to ablate neoplastic pancreatic tissue. We used an in vitro model to examine the effects of bone, metallic stents, plastic stents, metal plates, and cyst-like lesions on HIFU treatment.

Methods

HIFU was delivered to the phantom models implanted with foreign bodies, and the location, shape, and size of the ablated zones were evaluated.

Results

Bone and metallic plates reflected the ultrasound beam, shifting the ablation zone from the focal zone to the prefocal area. In the phantoms containing metal stent, plastic stent, and cyst, most of the ablative energy was reflected to the prefocal area by the surface, with the remainder penetrating through the phantom. The area of the ablated margins was significantly larger in size and volume than the intended focal ablation zone.

Conclusions

During HIFU therapy, artificial or anatomical barriers could affect the direction of the ultrasound beams, shifting the ablation zone from the focal area to a prefocal site with a larger than expected ablation zone. These factors should be considered prior to HIFU treatment for pancreatic tumors because they could limit ablation success, in addition to causing complications.     

Association of Depression and Suicidal Ideation with Unreasonable Patient Demands and Complaints Among Japanese Physicians: A National Cross-sectional Survey

Background  

Physicians' mental health can be affected by unreasonable demands and complaints made by patients.