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Aldose reductase (ALR2), the first enzyme of the polyol pathway, may plan an important role in the pathogenesis of diabetic microvascular complications. The gene coding for ALR2 has been localized to chromosome 7q35. Using an ALR2 probe in conjunction with the restriction endonuclease Bam-HI, we have investigated the ALR2 locus of 128 patients with type I diabetes. A significant decrease in the frequency of the 8.2 kilobase (kb) Bam-HI ALR2 genotype and 8.2 kb allele was found in patients with nephropathy (nephropaths) compared to those with retinopathy alone (retinopaths) (p0.05 and 0.25, respectively). We have previously shown that an RFLP of the T-cell antigen receptor constant beta-chain (TCRBC) locus, which is also localized to chromosome 7q35, is strongly associated with susceptibility to microvascular complications. The 128 patients were genotyped using the restriction endonuclease Bgl-II and a TCRBC probe. The 10/9.2-8.2 kb TCRBC-ALR2 genotype was significantly decreased in the nephropaths compared to the retinopaths (13.7% versus 43.6%, chi 2 = 10.1, p0.0025). The 10/9.2 and 9.2/9.2 kb TCRBC-ALR2 haplotypes were increased in the nephropaths compared to the retinopaths (32.5% versus 8.9% chi 2 = 10.9, p0.001). These results suggest that chromosome 7q35 harbors a gene(s) that is involved in the pathogenesis of microvascular complications. Interestingly, the gene coding for endothelial nitric oxide synthase has recently been localized to the same chromosomal region as ALR2.

Most researchers see industry careers as their future, and rightly so as there is more money and growth in industry compared to academia. At the beginning of our careers, most of us believe that research will not be much different, whether it is in an academic setting or industrial environment. But this is far from truth. In fact there is a world of difference between the 2 settings as illustrated by the following comparisons

Type I diabetes is strongly associated with the major histocompatibility complex (MHC) class II region (DR and DQ loci), and to a lesser extent the class III region (complement C4 loci). Restriction fragment length polymorphism analysis was employed to investigate the C4 and heat shock protein 70 (HSP70) loci of 176 patients with type I diabetes and 92 healthy controls. In the patient population there was an excess of deletions of the C4A locus (48.5% vs 22.1%, P less than 0.0005). The HSP70 probe in conjunction with the restriction endonuclease Pst I detects two alleles of 9 or 8.5 kilobases (kb). The 8.5 kb allele was significantly increased in the patient group compared to healthy controls (0.569 vs 0.353, respectively, P less than 0.0005). Furthermore, a C4A deletion nearly always occurred with the 8.5 kb HSP70 allele, suggesting that it may be a marker of the HLA-A1,B8,C4A deletion, DR3 extended haplotype.

Twenty-five patients (seven male, 18 female) were diagnosed as having the loin pain and haematuria syndrome. Presenting symptoms were either loin pain alone or pain associated with macroscopic or microscopic haematuria, and were longstanding, having been present for mean of 9.3 years in males, and 10 years in females. Ten patients described symptoms of passing gravel or renal stones but these were only demonstrated radiologically in two patients. Investigation of all patients showed anatomically normal renal tracts, normal renal function, and no significant proteinuria. Phase-contrast microscopy during episodes of haematuria revealed dysmorphic red cells in all 10 patients studied. Renal biopsies were performed in 20 patients and showed no glomerular pathology, but arteriolar and arterial hyalinosis was seen in 13 of 20 (65 per cent), fibro-elastosis in larger vessels in eight of 20 (40 per cent) and red blood cells in tubules in 13 of 20 (65 per cent) patients. The histological appearance in vessels was similar to that seen in cyclosporin A nephrotoxicity and would be consistent with the hypothesis that regional vasospasm occurs in the cortical circulation. Haematological studies in 22 patients, when compared with age and sex matched controls, showed the presence of circulating platelet aggregates, elevation of plasma beta-thromboglobulin (p less than 0.001), and increased platelet aggregation in response to serotonin and ADP (p less than 0.05 and p less than 0.03, respectively). Plasma concentrations of D dimer (p less than 0.02) and C-reactive protein (p less than 0.03) were also significantly elevated in the patient group. There was no deterioration of renal function during a mean observation period of 3.7 years and no patients developed proteinuria. Treatment was largely supportive; seven patients with intractable loin pain underwent surgical denervation with the relief of pain in four.

Blood rheology and haemostasis have been investigated in 8 haemodialysis patients during treatment with recombinant human erythropoietin (rHuEPO). The aim was to elucidate the mechanism by which rHuEPO improves haemostasis, and to determine whether rHuEPO promotes intravascular coagulation. Investigations were performed before, and after 3 months of treatment. Haemoglobin and haematocrit rose significantly after rHuEPO (p less than 0.001) and there was a concurrent shortening of the bleeding time. No significant changes were observed in platelet aggregation, thromboxane generation, or platelet nucleotide content during the treatment period. Whole blood viscosity increased following rHuEPO (p less than 0.01), but plasma viscosity and red cell deformability were unchanged, as were markers of intravascular platelet activation and plasma levels of cross-linked fibrin derivatives. No patient suffered from thrombosis during the study period, and elevation of the haematocrit in uraemic patients up to 0.35 with rHuEPO did not appear to lead to intravascular coagulation. Shortening of the prolonged bleeding time in haemodialyzed patients following rHuEPO appeared to be due to the increase in circulating red cells, rather than to changes in platelet reactivity.

To the Editor: Paul Hawken said, “All is connected…no one thing can change by itself.”1 The face of pharmacy is changing as the healthcare system itself changes. With the recent opportunity of reimbursement for cognitive services through Medicare Part D MTMS legislation, to the ongoing battle for the pharmacy dollar from the consumer with free or $4.00 generic prescriptions, to more pharmacies becoming full service healthcare centers and providing onsite clinical assessments, the evolution of pharmacy is rapidly morphing. These new opportunities are a mixture of good and less than good ideas for pharmacy as a profession. When thinking about other professional areas, what could pharmacy learn from others? More importantly, as pharmacy educators, how can we integrate different professions' thinking into our curriculum? Legal and Accounting. When was the last time you walked into your lawyer's office or your accountant's office, unannounced, without an appointment, and asked for immediate service? The answer to that question is most likely never. Nearly all other professions require appointments for consultative services. Pharmacy is one of the most trusted professions in the world; however, can we purvey quality services prn with unknown prescription dispensing demands, particularly in community practice? With MTMS now established, pharmacists should begin considering fee-for-service consultative appointments. It firmly establishes professional value with customers and provides the opportunity for uninterrupted, higher quality service for the patient. As educators, the more opportunities during IPPE and APPE we can expose students to regarding professional services by appointment, the more students will feel empowered to initiate this type of model into their practices after graduation. At Butler, we have brought in pharmacists performing such services by appointment and exposed students on community practice rotations to their ideas and thoughts, as we do not yet have enough sites for all students to experience such practice opportunities. Public Relations and Advertising. If you have ever had the opportunity to meet with a public relations or advertising representative for hire, the first thing they would show you is a portfolio of their work. With continuing professional development now on the horizon, there is every opportunity for pharmacists to begin providing the same to potential employers – a portfolio of their work. This could include not only a CV, but writing samples, a hero file with letters of recommendation, any certifications or classes taken (both CE and non CE), and annual performance reviews. Any recruiter will note that documentation in site will be much more tangible for visual learners and hiring managers. The method to integration of this portfolio idea into the curriculum could best be served by providing outside professionals with more experience in writing portfolios that share their ideas with pharmacy students. This could easily be integrated into a professional practice course or an Introduction to Advanced Pharmacy Practice Experiences course. Sales and Marketing. Pharmacists are in demand. The average student graduating still receives multiple offers for employment upon licensure. Students therefore do not have to market themselves actively for a job after college. Also, the major pharmacy chains are battling over pricing of prescriptions rather than focusing on high quality service or providing other ancillary services to their customers which in turn develops a unique market position for their companies. What if pharmacies took the Steve Jobs' approach to providing excellent, unique appointment-only service as a separate section within the retail store? Many Macintosh computer owners will never go back to a PC simply because of the unique genius bar service that is provided by appointment at each and every Mac computer store. Pharmacists and students need to understand they are selling themselves each and every day. Everyone has a unique brand. In the new economy, it is not the product, but the customer's experience that will make the inedible mark and keep the customer over the long term. Also, many pharmacists are incentivized for generic substitution. What if pharmacists proactively presented new generic switches to nearby physicians as a value-added professional service? We have addressed these issues at our institution with a new seminar series program that addresses marketing of a community-based pharmacy by bringing in pharmacists that have actually performed sales and marketing practices within their communities and offered discussions with students currently on community practice rotations about such practices. Teaching and Education. Theoretically, all pharmacists, not just pharmacists in academia, are educators. Not only do we have to learn a lot of scientific details, but we also have to be able to communicate those ideas back to the customer at a level relevant to the customer. All pharmacists can learn from reading and studying great educators. To be a great educator means that one must also be a great life-long learner. Moving beyond just continuing education to a broader scope of customized continuing professional development will provide more educational and intellectually challenging areas for pharmacists to master and in turn better serve their patients and profession. Also, as pharmacy educators, are we teaching our students how to teach others? Each pharmacy school should offer an academic rotation within advanced pharmacy practice experiences (APPEs) and require it for all students. Preceptors in this arena are easy to find, for they are teachers at schools of pharmacy. Coaching. Life coaches, wellness coaches, and business coaches are everywhere. In order to establish and foster long-term relationships with patients and retain business, pharmacists should focus on preventative services and coaching their patients around wellness rather than just discussing the treatment issues at hand with a prescription. Pharmacists are trained on how to help their patients create a wellness plan, a medication plan, long-term disease management plans and even diet and exercise plans for better health. At Butler University, we have APPEs for students in the campus wellness center called Healthy Horizons and directed by Dr. Carrie Maffeo. During this APPE, students check blood pressures, body composition, and perform other tests that expose them to the opportunity to coach patients in the realm of wellness without simultaneously focusing on dispensing. Entrepreneurs. Entrepreneurs tend to have a great combination of vision, technical knowledge, and ability to get things done. These are qualities from which any profession, including pharmacy, can benefit. Pharmacy used to be an entrepreneurial profession with independent community pharmacies being the rule rather than the exception in practice. However, we need to hold on to the entrepreneurial mindset firmly for future generations of pharmacists, as creativity and right-brained thinking will be the new commodity for employers in the years to come. At Butler, we have provided opportunities for students to not only create new over-the-counter products in the self-care course, but also assign them to “sell” their products to the class. Students need to understand the creative process in projects that not only allows them to break the ice among their team members, but more importantly, teaches them the creative process and the ability to think outside the box. Artists. Finally, each and every one of us has the ability to be an artist in whatever profession we have chosen. The common thread among all artists is passion. In The Reinvention of Work, author Matthew Fox explains, “Jobs are to work as leaves are to a tree. If the tree is ailing the leaves will fall.”2 He goes on to state the definition of the word job came from the Middle English word gobbe, which meant lump. Whereas, “work is about a role we play in the unfolding drama of the universe.” We need more rock stars in our profession. We should see them in the media, on television, on radio, online – talking about drugs and all the amazing pharmacology that we can best explain…no other profession provides as much training on pharmacology. According to Fox, by sharing our work, we share “part of our display, part of the parading of our beauty” in the universe. Our work is beautiful. Every university that has a communications department, television channel, or radio station along with a school of pharmacy should host a program with pharmacy students discussing hot topics in healthcare. This exposes them to media challenges and therapeutic challenges simultaneously. Students must be able to think on their feet and effectively communicate, as all in media must do. Pharmacy can learn a lot from other professions. The examples above are few of many others from which we can learn. By connecting to other professions and extracting their best practices, we have further opportunity to elevate ourselves. As we change, develop, and morph as a profession into the new millennium, those with the audacity to pioneer new and better ideas will ensure a profession that will not only evolve, but endure. Erin Albert, PharmD, MBA College of Pharmacy & Health Sciences Butler University

Tissue Microarrays (TMAs) have emerged as a powerful tool for examining the distribution of marker molecules in hundreds of different tissues displayed on a single slide. TMAs have been used successfully to validate candidate molecules discovered in gene array experiments. Like gene expression studies, TMA experiments are data intensive, requiring substantial information to interpret, replicate or validate. Recently, an open access Tissue Microarray Data Exchange Specification has been released that allows TMA data to be organized in a self-describing XML document annotated with well-defined common data elements. While this specification provides sufficient information for the reproduction of the experiment by outside research groups, its initial description did not contain instructions or examples of actual implementations, and no implementation studies have been published. The purpose of this paper is to demonstrate how the TMA Data Exchange Specification is implemented in a prostate cancer TMA. The Cooperative Prostate Cancer Tissue Resource (CPCTR) is funded by the National Cancer Institute to provide researchers with samples of prostate cancer annotated with demographic and clinical data. The CPCTR now offers prostate cancer TMAs and has implemented a TMA database conforming to the new open access Tissue Microarray Data Exchange Specification. The bulk of the TMA database consists of clinical and demographic data elements for 299 patient samples. These data elements were extracted from an Excel database using a transformative Perl script. The Perl script and the TMA database are open access documents distributed with this manuscript. TMA databases conforming to the Tissue Microarray Data Exchange Specification can be merged with other TMA files, expanded through the addition of data elements, or linked to data contained in external biological databases. This article describes an open access implementation of the TMA Data Exchange Specification and provides detailed guidance to researchers who wish to use the Specification.

Intelligent tutoring systems are sought to ease the imbalance created by higher demand of multi-disciplinary knowledge/skill transfer, and increasingly scarce resources in education. Configurable, Incremental and Re-structurable Contributive Learning Environments (CIRCLE) are constructed with the purpose of circumventing the problems of legacy intelligent tutoring systems and facilitates the increasing need of distance education. The two major components, integrated successfully into CIRCLE, are: 1) Plug-able Intelligent Tutor an ITS system that incorporates domain knowledge modules as and when they are available; 2) VRCapture, an authoring tool that is designed to capture the intricate and inter-related conceptual knowledge from the teacher/expert by using an ''input-by-example'' approach.

To further define the platelet abnormality responsible for uremic bleeding, we studied platelet aggregation with adenosine diphosphate, ristocetin, and collagen in serum fractions obtained by Sephadex G-15 chromatography. We found that uremic patients had considerable inhibition in several peaks of middle molecular range, but the findings were inconsistent and not clearly related to the degree of uremia.

Chemiluminescent molecules can be readily detected in the range 10 −15 to 10 −18 mol, and potentially at least down to 10 −20 mol reacting/s. The chemiluminescent compound aminobutylethylisoluminol (ABEI) and its isothiocyanate derivative have been synthesized. The ABEI was coupled to rabbit immunoglobulin and cyclic AMP. These labeled antigens were stable for at least 9 months and were used to establish chemiluminescent immunoassays. When these chemiluminescent-labeled antigens bound to their respective fluorescein-labeled antibodies, a wavelength shift towards the green was detected in the chemiluminescence. This was due to chemiluminescence energy transfer and used to establish an homogeneous immunoassay which could measure these antigens in biological samples at least as sensitively as conventional radioimmunoassays.

During a nine-month period 43 consecutive infants who needed exchange transfusions for the management of their hyperbilirubinemia randomly received whole blood less than 5 days old (control group) or frozen erythrocytes diluted in plasma (experimental groups). There was no different prior to and after exchange transfusions in total protein, albumin, globulin, immunoglobulins, bilirubin, and hematocrit in the control group versus the experimental group. The efficacies of bilirubin removal, as measured by delta bilirubin, were the same in the two groups. Advantages of exchange transfusion with freeze-preserved erythrocytes suspended in type-specific plasma are discussed.