A human xenograft model for testing early events of epithelial neoplastic invasion

We report on a model of human prostate tumor cell invasion using the SCID (severe combined immunodeficient) mouse diaphragm. Tumor cells were injected into SCID mice intraperitoneally and the diaphragms harvested three to five weeks later. Electron microscopy showed tumor cell penetration of the mesothelial cell layer and adhesion to the underlying basement membrane on the inferior surface of the mouse diaphragm, where colonies developed. Immunohistochemistry showed invasion by tumor cells through the basement membrane into the muscle of the diaphragm, presence of human tumor cells among the muscle cells and the presence of selected proteins on the invasion front of the tumor cells. Digital image analysis enabled quantitative comparison of events in the metastatic cascade by variants of the tumor cell line and evaluation of the effectiveness of a putative tumor inhibitor. Results suggest that the SCID mouse diaphragm model is a convenient, effective, easily oriented and reproducible in vivo model of the early events associated with human prostate tumor cell invasion.     

IMPACTED RIGHT UPPER CENTRAL INCISOR AND TRANSPOSITION OF TWO OTHER ANTERIOR TEETH ON THE SAME SIDE (A Case Report)

A young boy presented with an uncommon finding of impaction of upper right central incisor and transposition of canine and lateral incisor on the same side. Esthetic management of his cosmetic problem which included fixed appliance therapy followed by light cure restorations is discussed.KEY WORDS: Impaction, Transposition     

The Trent Regional Day Case Commission. An initiative to investigate the constraints to the extension of the use of day surgery

In 1989, Trent Regional Health Authority set up a Commission to enquire into the organization of day case surgery and encourage its use. Improved methods for measuring and comparing day surgical activity were developed using routine data sources. These revealed even greater variation between hospitals and specialties in the amount of day surgery performed than did the usual analyses. Arrangements for day surgery differed considerably between specialties. Few theatres, beds, or surgeons' sessions were dedicated to day surgery, but general surgery and gynaecology used dedicated facilities more than other specialties such as ENT and ophthalmology. The Commission visited each hospital and found that day case facilities, organization and resources were poor in many of them. It was able to make specific recommendations for improvements. Day case surgery increased substantially over the period that the Commission operated, most hospitals reported that it had influenced changes in day surgery and that it had been useful, especially for local managers. Schemes to increase day surgery were funded. Highlights two elements for managing change: the need for good information about a problem, and the need to extend ownership of the issue throughout the organization.     

Size at birth and blood pressure at 3 years of age. The Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC)

The relations between size at birth and blood pressure were examined in a population-based longitudinal study of pregnancy and childbirth in the English county of Avon (the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC)) in 1994-1996. A total of 1,860 singleton children aged 3 years (response rate = 74%) were studied. Both height and body mass index were strongly related to blood pressure. After adjustment for current height and body mass index, birth weight showed a graded inverse relation with both systolic (-1.91 mmHg/kg, 95% CI -2.61 to -1.21 mmHg/kg, p < 0.0001) and diastolic blood pressure (-1.42 mmHg/kg, 95% CI -1.96 to -0.88 mmHg/kg, p < 0.0001) which was similar in boys and girls. Although birth length, head circumference, and ponderal index at birth were also inversely related to blood pressure, these relations disappeared after adjustment for birth weight. The strength of the birth weight-blood pressure relation was not strongly influenced by maternal height or by weight gain in the first year after birth, but was particularly strong in children who were shortest at 3 years of age. While the association between birth weight and blood pressure is consistent with reports from many earlier studies, the absence of independent relations between other measures of size at birth (particularly length:head circumference and ponderal index) and blood pressure does not suggest that undernutrition at a critical period of fetal growth plays an important role. Moreover, accelerated postnatal growth does not seem to underlie the birth weight-blood pressure association.     

Effectiveness of a social influences smoking prevention program as a function of provider type, training method, and school risk

OBJECTIVES: This study determined the effect of provider (nurse or teacher) and training method (workshop or self-preparation) on outcomes of a social influences smoking prevention program. METHODS: One hundred elementary schools were stratified by school risk score (high risk = high smoking rate among senior students) and assigned randomly to conditions: (1) teacher/self-preparation, (2) teacher/workshop, (3) nurse/self-preparation, (4) nurse/workshop, and (5) control. Intervention occurred in grades 6 to 8. Smoking status at the end of grade 8 was the primary endpoint variable. RESULTS: Intervention reduced grade 8 smoking rates in high-risk schools (smoking rates of 26.9% in control vs 16.0% in intervention schools) but not in low-risk schools. There were no significant differences in outcome as a function of training method and no significant differences in outcome between teacher-provided and nurse-provided interventions in high- and medium-risk schools. Although nurses achieved better outcomes than did teachers in low-risk schools, neither provider type achieved outcomes superior to the control condition in those schools. CONCLUSIONS: Workshop training did not affect outcomes. Teachers and nurses were equally effective providers. Results suggest that programming should target high-risk schools.     

Oxidation of cytosolic proteins and expression of creatine kinase BB in frontal lobe in different neurodegenerative disorders

The presence of the biomarkers of oxidative damage, protein carbonyl formation and the inactivation of oxidatively sensitive brain creatine kinase (CK BB, cytosolic isoform), were studied in frontal lobe autopsy specimens obtained from patients with different age-related neurodegenerative diseases: Alzheimer's disease (AD), Pick's disease (PkD), diffuse Lewy body disease (DLBD), Parkinson's disease (PD), and age-matched control subjects. The CK activity was significantly reduced in the frontal lobe of AD, PkD and DLBD subjects, and CK BB-specific mRNA was significantly reduced in AD and DLBD. Protein carbonyl content was significantly increased in AD, PkD and DLBD. The results of this study confirm that the presence of biomarkers of oxidative damage is related to the presence of histopathological markers of neurodegeneration. Our data suggest that oxidative damage contributes to the development of the symptoms of frontal dysfunction in AD, PkD and DLBD. The development of frontal dysfunction in idiopathic PD might be secondary to oxidative damage and neuronal loss primarily located in the nigrostriatal system. The results of CK BB expression analysis demonstrate that the loss of the isoenzyme in different neurodegenerative diseases is likely the consequence of its posttranslational modification, possibly oxidative damage. Changes in CK BB expression may be an early indicator of oxidative stress in neurons.     

First principles investigation of singly reduced cytochrome P450.

1. The application of novel ab initio quantum mechanical methods to the states in the catalytic cycle of cytochrome P450 following the first reduction step is described. 2. A good correlation was found between the calculated energy of reduction and the experimentally determined redox potential for a range of substrate- and substrate analogue-bound systems. 3. On reduction of the haem system, the ground state of Fe remains Fe3+. On binding of a CO molecule, Fe adopts a low-spin Fe2+ state, in agreement with experiment. However, on binding of an O2 molecule, calculations indicate that the system adopts a ferric superoxide ground state, in which the Fe is in a low-spin Fe3+ state.     

An evaluation of increasing doses of ranitidine for treatment of heartburn

BACKGROUND: This was a randomized, double-blind, placebo-controlled, multicentre, parallel group, dose-ranging trial of ranitidine tablets for relief of episodic heartburn. Adult out-patients who reported heartburn relieved by antacids at least seven times per week were eligible. METHODS: Patients who successfully completed a 1-week single-blind placebo run-in phase and who did not achieve adequate relief in more than 50% of heartburn episodes were randomized to a 1-week, double-blind treatment phase during which they received ranitidine doses of 25, 75 or 125 mg, or placebo. RESULTS: Of 577 patients randomized, 566 had at least one evaluable heartburn episode and were included in the intention-to-treat analysis. All three ranitidine doses were statistically significantly superior to placebo in providing overall episodic heartburn relief for the first episode (P < 0.002), last episode (P相似文献   

A double-blind, placebo-controlled study of the efficacy and safety of non-prescription ranitidine 75 mg in the prevention of meal-induced heartburn

BACKGROUND: Ranitidine 75 mg (Zantac 75) has been shown to be effective for the treatment of pre-existing heartburn symptoms. AIM: To compare the efficacy of dosing ranitidine 75 mg or placebo 30 min prior to a proven heartburn-provoking meal in completely preventing or reducing subsequent heartburn symptoms. METHODS: A randomized, double-blind, parallel methodology was used at nine investigative centres. Following a screening visit, patients ate a standard test meal consisting of chili, chips and a soft drink on two occasions. On the first occasion, patients received single-blind placebo 30 min before the meal. This meal was used to qualify patients and to ensure the onset of a minimum level of heartburn. Patients who qualified were randomized (n = 284) to receive double-blind ranitidine 75 mg or placebo 30 min before a second test meal administered 4-14 days later at the treatment visit. Patients recorded whether heartburn was present and rated heartburn severity by completing visual analogue scales at 15-min intervals over the 4. 5 h meal evaluation periods. RESULTS: Statistically significant differences favouring ranitidine 75 mg were determined for complete prevention of heartburn (P < 0.006), heartburn severity area under the curve (P < 0.001), a clinical success end-point (P < 0.001), and all other end-points (P < 0.001). CONCLUSIONS: These data clearly demonstrate that ranitidine 75 mg is effective in completely preventing or decreasing heartburn when administered 30 min prior to a provocative meal.