Bisphosphonate therapy in an infant with generalized arterial calcification with an ABCC6 mutation.

Generalized arterial calcification of infancy (GACI) is a rare genetic disorder with high infantile mortality, described to be due to ENPP1, and less commonly ABCC6 mutations. Bisphosphonate treatment has been described to improve survival in ENPP1-positive GACI patients, but few studies have described bisphosphonate treatment in ABCC6-positive patients. Without therapy, patients will die before 6 months of age. Our patient is now 3 years old, former recipient twin of twin-to-twin transfusion syndrome (TTTS). Initial fetal echocardiogram at 19 weeks showed calcifications of the ascending aorta and pulmonary artery (PA). She underwent utero laser therapy, and despite resolution of the TTTS, her follow-up scans showed progressive calcification of the aorta and PA. Postnatal echocardiogram showed calcification and supravalvar stenosis of the aorta and PA. CT on day of life 6 showed calcifications in the PAs, aortic arch, and descending aorta. Quantification of valvular calcification can be difficult; in our patient, increasing outflow tract gradient on echocardiogram was used to monitor disease progression. Molecular testing revealed an ABCC6 gene mutation. She was started on weekly IV pamidronate (0.1-0.3 mg/kg/week) on day 8 of life then transitioned to oral etidronate (15-20 mg/kg/day). Given progressive supravalvar aortic and pulmonary stenosis, she underwent surgical repair with patch augmentation of the PA and ascending aorta at 4 months old. She has done well post-operatively, continuing on enteral bisphosphonate therapy with no side effects to date. Her identical twin was confirmed to have the same mutation and remains asymptomatic with no calcifications. Aggressive bisphosphonate therapy should be started as soon as possible in patients with infantile arterial calcinosis due to ABCC6 or ENPP1 mutations. Echocardiographic evaluation can be used to monitor disease progression by arterial gradients. Molecular testing is also essential to evaluate for possible co-morbidities in these patients and pregnancy management for the future.

Leading beyond the bottom line, Part 4. The questions it has raised.

The Leading Beyond the Bottom Line article series has received an overwhelming response from ACPE members, mostly in enthusiastic support of this new leadership concept. Some of the important questions raised by members are presented with answers from the authors. This article also explores the moral challenge of leadership and why health care is more than a business. In recent years, there's been confusion about the role of the health care enterprise, its leadership and its management. We have lost our way about the "moral" thing, the "right" thing, because we have no philosophy to guide us. To manage or lead in this "business" of health care, a philosophy is required that recognizes the multiple elements to which the leader has responsibility and obligations: the customers, community, employees, and, certainly, the financial assets.

Leading beyond the bottom line.

Do physician executives approach managing and leading health care organizations like a CEO of a Fortune 100 company? Or does their training as physicians first give them a unique perspective, leading them to view organizational issues differently? The authors suggest that to be a physician executive is to be the practitioner, teacher, coach, and mentor for a new philosophy of leadership and management called Leading Beyond the Bottom Line. While the financial health of an organization is critical to its survival and its ability to fulfill its purpose, the trap is to focus on maximizing the bottom line. This new philosophy leads an organization to attend in equal measure to the (1) welfare of its patients, (2) its financial health, (3) the well-being of its employees, and (4) the building of its community. "The Optimal Organization" is one in which these four objectives are seen not only as related, but interconnected, and the goal is to maximize all of them. The legitimate role of the physician executive is to manage in search of Pareto Optimum, or the maximum benefit for all four organizational objectives. Clearly, this is a tougher job than maximizing profits or just optimizing profits and patient care.

Leading beyond the bottom line: organizational assets for the new economy. 2.

Organizations are created to aggregate resources to accomplish some purpose, be it to provide health care, raise a family, or build cars. These resources are assets. A manager has a fiduciary responsibility, by practice, and, in many cases, by law, to make the best use of those assets. Traditionally, we've evaluated the use of assets through financial statements. The troublesome aspect of these financial statements is that they were designed to measure only those things that can be counted simply--financial and physical assets. But our world has moved from an industrial, manufacturing age to an information, service economy and we are learning that intangible assets are as powerful--potentially more powerful--in creating value as are tangible assets. Recognizing the intangible asset value of employees, customers, and the community is the challenge in this new service economy. Effective health care leaders need to leverage and manage all of an organization's assets.

Lack of an association between polymorphisms of the T-cell receptor alpha-chain and ulcerative colitis.

It was recently reported that, using a T-cell receptor alpha-chain complementary deoxyribonucleic acid probe (pGA5) and the restriction enzyme Eco RV, a 10-kilobase restriction fragment length polymorphism was detected significantly more frequently in patients with ulcerative colitis than in patients with Crohn's disease and controls. This finding had great potential importance, as no gene marker had previously been found to be strongly associated with inflammatory bowel disease. Therefore, an attempt to confirm it in an independent laboratory and patient population has been made in this study. Thirty patients with ulcerative colitis, 30 with Crohn's disease, and 30 healthy control subjects were studied using the Eco RV restriction enzyme and the same T-cell receptor alpha-chain complementary deoxyribonucleic acid probe as was used in the prior report. No 10-kilobase fragment or any other polymorphism using this probe-enzyme combination was found in any of the individuals studied. Polymorphisms were observed with the restriction enzyme Bgl II, but their frequencies did not distinguish between cases and controls. Therefore, there is as yet no evidence for an association between polymorphisms of Eco RV-digested genomic DNA probed with the pGA5 T-cell receptor alpha-chain complementary deoxyribonucleic acid and the predisposition to inflammatory bowel disease.

Achondroplasia with ankylosing spondylitis.

A 41-year-old-white man with achondroplasia has been followed intermittently since age 27. During this time, he has complained of neck and back pain with limited mobility in both. Other problems have included temporomandibular joint pain, dysuria without apparent urinary tract infection iritis, anemia, and an elevated gamma globulin fraction. Recently he returned to the clinic complaining of rigidity of the entire spine. Radiographs showed complete fusion of the sacroiliac joints and fusion of the cervical vertebral bodies and apophyseal joints, consistent with ankylosing spondylitis. He was found to be HLA B-27 positive. This case illustrates the importance of considering other diseases whenever atypical orthopedic problems arise in patients with a bone dysplasia.