Model Features of a Cardiac lontophoretic Drug Delivery Implant

Pharmaceutical Research -     

Double skin island pectoralis major myocutaneous flap with nipple-areola complex preservation: a case report.

A horizontal double skin island pectoralis major myocutaneous flap with preservation of nipple-areola complex is described, a different modification used to reconstruct a complex defect following radical resection of a locally advanced gingival carcinoma. The skin islands are horizontally separated by a distance of 2.5 cm but rely on one vascular pedicle for their blood supply. The muscle between the skin islands provides the soft tissue bulk between the internal mucosal and external skin lining. The need for a separate segmental flap or a split-thickness skin graft for mucosal lining was eliminated.     

Spatial low frequency pattern analysis in positron emission tomography: a study between normals and schizophrenics.

Using the two-dimensional Fourier transform and the brain's centroidal principal axis, a method is developed for the analysis of PET metabolic brain images without the use of predefined anatomic regions of interest. We applied the method to images from a group of 11 normal and 12 medicated schizophrenics tested under resting conditions and under a visual task. A cortical/subcortical spatial pattern was found to be significant in two directions; anterior/posterior and chiasmatic (left-anterior/right-posterior). The best individual clinical classification (Jackknife classification) occurred under visual task at two axial brain levels: at the basal ganglia with correct classification rates of 91% and 84%, while the cerebellum had rates of 82% and 92%. These high classification rates were obtained using only the four coefficients of the lowest spatial frequency. These results point to the generalized brain dysfunction of regional glucose metabolism in chronic medicated schizophrenics both at rest and at a visual image-tracking task.     

Metabolic, molecular genetic and toxicological aspects of the acetylation polymorphism in inbred mice.

Over the past 10 years, much fascinating information has been obtained concerning the biochemistry, genetics, toxicological implications and molecular genetics of the N-acetylation polymorphism in mice. Using C57BL/6J (B6) mice as representative of rapid acetylation and A/J (A) mice as representing slow acetylation, it has been shown that the polymorphism observed in N-acetyltransferase (NAT) activity in liver also occurs in kidney, bladder, blood, and other tissues. The development of congenic acetylator mouse lines derived from B6 and A, have provided the necessary tools to study the role of the acetylation polymorphism, on either the B6 or A genetic background, free of nearly all other genetic differences between these strains. Eliminating genes which modify and complicate the differences due to the acetylator genes make the congenic lines very useful in toxicology studies, particularly those involving carcinogenesis. The molecular genetic basis of the acetylator polymorphism in B6 and A mice involves two Nat genes. Nat-1 encodes a protein termed NAT1 which is identical in rapid and slow acetylator strains. Nat-2, however, differs between rapid and slow strains by a single nucleotide change in the coding region. The corresponding NAT2 proteins differ by a single change at amino acid 99: an hydrophilic asparagine in rapid acetylator NAT2 to an hydrophobic isoleucine in NAT2 from slow acetylators. The mechanistic basis for the differences between rapid and slow acetylation in mice appears to be that NAT2 from the rapid B6 strain is 15-fold more stable at 37 degrees C and is transcribed/translated with a maximal efficiency twice that of the enzyme from slow acetylator A mice. Results discussed in this review indicate that mice provide an excellent system for studying the N-acetyltransferase polymorphism and also are useful for modelling several aspects of the human N-acetyltransferase polymorphism.     

A method for assessing quality of control from glucose profiles.

AIM: As the practice of multiple assessments of glucose concentration throughout the day increases for people with diabetes, there is a need for an assessment of glycaemic control weighted for the clinical risks of both hypoglycaemia and hyperglycaemia. METHODS: We have developed a methodology to report the degree of risk which a glycaemic profile represents. Fifty diabetes professionals assigned risk values to a range of 40 blood glucose concentrations. Their responses were summarised and a generic function of glycaemic risk was derived. This function was applied to patient glucose profiles to generate an integrated risk score termed the Glycaemic Risk Assessment Diabetes Equation (GRADE). The GRADE score was then reported by use of the mean value and the relative percent contribution to the weighted risk score from the hypoglycaemic, euglycaemic, hyperglycaemic range, respectively, e.g. GRADE (hypoglycaemia%, euglycaemia%, hyperglycaemia%). RESULTS: The GRADE scores of indicative glucose profiles were as follows: continuous glucose monitoring profile non-diabetic subjects GRADE = 1.1, Type 1 diabetes continuous glucose monitoring GRADE = 8.09 (20%, 8%, 72%), Type 2 diabetes home blood glucose monitoring GRADE = 9.97 (2%, 7%, 91%). CONCLUSIONS: The GRADE score of a glucose profile summarises the degree of risk associated with a glucose profile. Values < 5 correspond to euglycaemia. The GRADE score is simple to generate from any blood glucose profile and can be used as an adjunct to HbA1c to report the degree of risk associated with glycaemic variability.     

Efficacy of continuous subcutaneous insulin infusion in Type 1 diabetes: a 2-year perspective using the established criteria for funding from a National Health Service.

AIM: To determine the 2-year efficacy of continuous subcutaneous insulin infusion (CSII) following the current established criteria for funding of a National Health Service. METHODS: Longitudinal, prospective, observational unicentre study. Included in the study were 153 Type 1 diabetes (T1D) subjects, previously treated with multiple daily injections (MDI) of insulin, in whom CSII was started in accordance with the criteria for reimbursement of the Catalan National Health Service. At baseline, we recorded data on age, gender, duration of the disease, body mass index (BMI), insulin dose and indications for CSII. Glycated haemoglobin (HbA(1c)) and the frequency of hypoglycaemic events were used to assess glycaemic control. Quality of life was assessed using three different self-report questionnaires. After 24 months, these same items were remeasured in all subjects. Serious adverse events and injection-site complications were also recorded. RESULTS: In 96% of subjects, CSII indication included less than optimal glycaemic control using MDI. HbA(1c) fell from 7.9 +/- 1.3 to 7.3 +/- 1.1% (P < or = 0.001) after 24 months of CSII. Insulin requirements were significantly lower at the end of follow-up (0.55 +/- 0.21 U/kg body weight) in comparison with before use of CSII (0.70 +/- 0.20, P < or = 0.001). BMI increased from 24.0 +/- 3.1 to 24.4 +/- 3.2 kg/m(2) after 24 months (P < or = 0.025). The rate of episodes of diabetic ketoacidosis per year remained unchanged. Mild and severe hypoglycaemic episodes were significantly reduced. The scores in all subsets of the Diabetes Quality-of-Life (DQoL) questionnaire significantly improved after 24 months of CSII. CONCLUSIONS: CSII, commenced according to the criteria for a nationally funded clinical programme, improves glycaemic control and quality-of-life outcomes with fewer hypoglycaemic episodes in T1D subjects previously conventionally treated with MDI.