A not-so-basic case of metabolic alkalosis: an analysis featuring Leendert Paul and emphasizing Occam’s razor

A patient had the onset of a severe degree of metabolic alkalosis associated with a very large daily loss of diarrheal fluid. Because the expected acid-base disorder in this setting is metabolic acidosis, factors that could result in the markedly increased concentration of bicarbonate (HCO₃⁻) in plasma (P ₃) were sought. In our approach, there is an emphasis on electroneutrality, mass balance, a quantitative analysis, and the application of basic concepts in physiology at the bedside. We suggest that there were 3 major factors that could explain why the P ₃ was so high. First, a severe degree of extracellular fluid volume contraction was probably the most important factor that raised her P ₃. Second, there may have been an unusual way to have an electroneutral addition of HCO₃⁻ and removal of chloride ions from her extracellular fluid compartment. Third, the diarrheal fluid could have contained little HCO₃⁻ because of a down-regulated intestinal secretion of HCO₃⁻. This analysis challenges the traditional pathophysiology of metabolic alkalosis.     

Pediatric Transplantation in the United States, 1995–2004

This article reviews trends in pediatric solid organ transplantation over the last decade, as reflected in OPTN/SRTR data. In 2004, children younger than 18 years made up nearly 3% of the 86 378 candidates for organ transplantation and nearly 7% of the 27 031 organ transplant recipients. Children accounted for nearly 14% of the 7152 deceased organ donors. The transplant community recognizes important differences between pediatric and adult organ transplant recipients, including different etiologies of organ failure, surgical procedures that are more complex or technically challenging, effects of development on the pharmacokinetic properties of common immunosuppressants, unique immunological aspects of transplant in the developing immune system and increased susceptibility to posttransplant complications, particularly infectious diseases. For these reasons, and because of the impact of end-stage organ failure on growth and development, the transplant community has generally provided pediatric candidates with special consideration in the allocation of deceased donor organs. Outcomes following kidney, liver and heart transplantation in children often rank among the best. This article emphasizes that the prospects for solid organ transplantation in children, especially those aged 1–10 years are excellent. It also identifies themes warranting further consideration, including organ availability, adolescent survival and challenges facing pediatric transplant clinical research.     

Thoracic Organ Transplantation in the United States, 1995–2004

This article reviews trends in thoracic organ transplantation based on OPTN/SRTR data from 1995 to 2004. The number of active waiting list patients for heart transplants continues to decline, primarily because there are fewer patients with coronary artery disease listed for transplantation. Waiting times for heart transplantation have decreased, and waiting list deaths also have declined, from 259 per 1000 patient-years at risk in 1995 to 156 in 2004. Fewer heart transplants were performed in 2004 than in 1995, but adjusted patient survival increased to 88% at 1 year and 73% at 5 years. Emphysema, idiopathic pulmonary fibrosis and cystic fibrosis were the most common indications among lung transplant recipients in 2004. Waiting time for lung transplantation decreased between 1999 and 2004. Waiting list mortality decreased to 134 per 1000 patient-years at risk in 2004. One-year survival following transplantation has improved significantly in the past decade. The number of combined heart-lung transplants performed in the United States remains low, with only 39 performed in 2004. Overall unadjusted survival, at 58% at 1 year and 40% at 5 years, is lower among heart-lung recipients than among either heart or lung recipients alone.     

Immunosuppression: Evolution in Practice and Trends, 1994–2004

Over the last 10 years, there have been important changes in immunosuppression management and strategies for solid-organ transplantation, characterized by the use of new immunosuppressive agents and regimens. An organ-by-organ review of OPTN/SRTR data showed several important trends in immunosuppression practice. There is an increasing trend toward the use of induction therapy with antibodies, which was used for most kidney, pancreas after kidney (PAK), simultaneous pancreas-kidney (SPK) and pancreas transplant alone (PTA) recipients in 2004 (72–81%) and for approximately half of all intestine, heart and lung recipients. The highest usage of the tacrolimus/mycophenolate mofetil combination as discharge regimen was reported for SPK (72%) and PAK (64%) recipients. Maintenance of the original discharge regimen through the first 3 years following transplantation varied significantly by organ and drug. The usage of calcineurin inhibitors for maintenance therapy was characterized by a clear transition from cyclosporine to tacrolimus. Corticosteroids were administered to the majority of patients; however, steroid-avoidance and steroid-withdrawal protocols have become increasingly common. The percentage of patients treated for acute rejection during the first year following transplantation has continued to decline, reaching 13% for those who received a kidney in 2003, 48% of which cases were treated with antibodies.     

Kidney and Pancreas Transplantation in the United States, 1995–2004

This article examines OPTN/SRTR data on kidney and pancreas transplantation for 2004 and the previous decade, and discusses recent changes in kidney-pancreas (KP) allocation policy and emerging issues in kidney donation after cardiac death (DCD). Although the number of kidney donors continues to increase, new waiting list registrations again outpaced the number of kidney transplants performed, rising by 11% between 2003 and 2004 and contributing to a 1-year increase of 8% in the number of patients active on the waiting list. DCD has increased steadily since 2000; 39% more DCD transplants were performed in 2004 than 2003. Both deceased donor and living donor kidney graft survival rates remain excellent and are improving. The number of people living with a functioning kidney transplant doubled between 1995 and 2004, to 101 440 with a functioning kidney-alone and 7213 with a functioning KP. Health care providers in all settings are more likely to be exposed to these transplant recipients. Patient survival following simultaneous pancreas-kidney (SPK) transplantation is excellent and has improved incrementally since 1995; death rates in the first year fell from 60 per 1000 patient-years at risk in 2001 to 45 in 2003. The number of solitary pancreas transplants increased dramatically in 2004.     

Liver and Intestine Transplantation in the United States, 1995–2004

Three years of survival data are now available and the impact of the model for end-stage liver disease (MELD) allocation system is becoming clear. After a decline in new registrants to the waiting list in 2002, the number increased to 10 856 new patients in 2004. Since the implementation of MELD, the percentage of patients who have been on the list for 1–2 years has declined from 24% to 19%. There has been a shift upward in the percentage of patients with higher MELD scores on the waiting list.
An increasing percentage of adult living donor liver recipients are over the age of 50 years; from 1% in 1997 to 51% in 2004. Parents donating to children (93% of living donors in 1995), represented only 14% in 2004. Long-term adjusted patient survival declined with increasing recipient age in adults following either DDLT or LDLT.
Cirrhosis caused by chronic hepatitis C virus (HCV) is the leading indication for liver transplantation and is associated with reduced long-term survival in recipients with HCV compared to those without HCV, 68% at 5 years compared to 76%.
Although the intestine waiting list has more than doubled over the last decade, an increasing number of centers now perform intestinal transplantation with greater success.     

Organ Donation and Utilization, 1995–2004: Entering the Collaborative Era

Continued progress in organ donation will help enable transplantation to alleviate the increasing incidence of end-stage organ disease. This article discusses the implementation and effect of the federally initiated Organ Donation Breakthrough Collaborative; it then reviews organ donation data, living and deceased, from 1995 to 2004. It is the first annual report of the Scientific Registry of Transplant Recipients to include national data following initiation of the collaborative in 2003. Prior to that, annual growth in deceased donation was 2%–4%; in 2004, after initiation of the collaborative, deceased donation increased 11%. Identification and dissemination of best practices for organ donation have emphasized new strategies for improved consent, including revised approaches to minority participation, timing of requests and team design. The number of organs recovered from donation after cardiac death (DCD) grew from 64 in 1995 to 391 in 2004. While efforts are ongoing to develop methodologies for identifying expanded criteria donors (ECD) for organs other than kidney, it is clear DCD and ECD raise questions regarding cost and recovery. The number of living donor organs increased from 3493 in 1995 to 7002 in 2004; data show trends toward more living unrelated donors and those providing non-directed donations.     

Breast Cancer in the Middle Eastern Population of California, 1988–2004

Abstract:  This report presents the patterns of incidence, survival, and mortality of breast cancer in the Middle Eastern (ME) population of California. Cases were identified through surname recognition and population estimates were obtained from census public use files. Rates, trends, and survival in this ethnic group were compared with the non-Hispanic White (NHW) of California, as well as natives in the Middle East. Age-adjusted incidence rates for the insitu (22.8), invasive (126.2), and mortality (23.2) in ME women were significantly lower than similar rates of 26.0, 146.9, and 30.6 in the NHW women. Incidence rate in ME women in California was higher than rates in women in the Middle East. Lower rates for early stage and higher rates for late stage diagnoses in this ethnic population suggest lack of optimal access to preventive healthcare. Relative survival in the two groups is negatively associated with stage at diagnosis and is slightly higher in ME women, probably due to large numbers of lost to follow-up in ME women suggesting the presence of salmon bias. Positive association with socioeconomic standing was detected only in the NHW women. Incidence of breast cancer in ME men was significantly higher than that of NHW men.     

Paul Galmiche (1914–2004)

Sans résumé