A survey of nine years heart transplantation at Erasme Hospital, University of Brussels.

Between March 1982 and March 1991, 225 heart transplantations (HTx) have been performed in 220 patients suffering end stage cardiac disease. Thirteen percent were females and 87% were males. Age range was from 5 to 68 years. The underlying cardiac disease was ischemic cardiopathy in 51.5%, congestive dilated cardiomyopathy in 42%, valvular cardiomyopathy in 3.5%, toxic myocarditis (post-adriamycin) in 1.5% and chronic rejection in 2.5% (retransplantation). Selection of the recipients was done following the currently well established criteria also taking into account the absolute major contraindications for HTx. Due to the still increasing demand of donor organs, currently donor age has been extended up to 50 years for male and 55 years for female donors. One quarter of the grafts were harvested on site in our institution, two other quarters were harvested somewhere else in Belgium and the last quarter provided by other countries cooperating with Eurotransplant. All patients have undergone orthotopic cardiac transplantation using the standard Lower and Shumway technique. Immunosuppression protocols have changed four times throughout the years. Nevertheless all were based on the use of Ciclosporine variously combined with other current immunosuppressive drugs. Rejection monitoring relied on routine endocardiac biopsy and was diagnosed according to the Billingham criteria. The in-hospital mortality is currently 11%. Infection, early right heart graft failure and acute rejection were the leading causes of death. The major causes of early morbidity were several curable infections, reversible rejection episodes, transient acute renal failure and controllable arterial hypertension. Among the survivors followed for at least one month up to nine years, half of late mortality was caused by chronic rejection followed by infection, sudden death, metabolic disorders, stroke and malignancy. Late morbidity involves cases of mild coronary graft diseases, biological renal insufficiency, some degree of arterial hypertension, dislipidemia. Current actuarial survival rate is 87% at one year, 76% at 5 years up to 9 years. Our experience confirms that HTx represents today and effective therapy for selected patients suffering end stage cardiac disease.     

Associations between haptoglobin polymorphism, lipids, lipoproteins and inflammatory variables

The haptoglobin allele frequencies and the phenotype distribution were determined in 741 male Caucasian workers, aged 35 to 59 years. The association of the haptoglobin polymorphism with various clinical and biochemical parameters was investigated. Furthermore a possible interaction with the apo E polymorphism on lipid and lipoprotein traits was analysed. The frequency of Hp1 and Hp2 was found to be 0.401 and 0.599, respectively. The observed distribution of Hp types (Hp 1-1, 15.5%; Hp 2-1, 49.3%; Hp 2-2, 35.2%) was in Hardy-Weinberg equilibrium. Age, body mass index, smoking, alcohol intake and blood pressure were comparable between the three Hp groups. Subjects with Hp 2-2 had significantly higher serum total and free cholesterol concentration compared to those in other haptoglobin types (P = 0.006 and P = 0.003). Similarly, apo B levels were significantly higher among Hp 2-2 individuals (P = 0.02). No significant differences were demonstrated between the Hp phenotypes in HDL cholesterol, apo A-I, apo E, Lp(a), cholesteryl esters, fibrinogen and C-reactive protein concentrations, although for the latter an increase was noticed in Hp 2-2. The effects of Hp type and apo E type on Lp(a) and on free cholesterol levels were found to be significantly multiplicative, with the highest free cholesterol values observed in subjects having Hp 2-2 and the apo epsilon4 allele. Significantly lower Lp(a) levels were observed in individuals carrying Hp 1-1 and an epsilon2 allele than in subjects without the epsilon2 allele. In conclusion, haptoglobin polymorphism may play an important role in the regulation of lipoprotein metabolism and could contribute to the risk of coronary heart disease. Larger samples are needed to clarify the clinical relevance of the gene-gene (Hp-apo E) interaction on lipids and lipoproteins.     

Pitfalls in the determination of common analytes in the critically ill

In the critically ill, the pre-analytical aspects of blood gas analysis still require attention from the clinician. Sampling and transport remain critical factors. Use of drugs may create analytical interferences for common analytes like glucose and protein. Icterus may falsely reduce creatinine and albumin values. Changes in the serum or plasma matrix (reduction of protein, increased covolume of solutes, ...) may furthermore cause important effects on the distribution of electrolytes. Enzyme activity measurements may be erroneous due to lack of essential oligoelements or reducing substances. Immunoassays may suffer from interferences caused by auto-antibodies. In case of hemolysis, a careful interpretation of test results is mandatory.     

A Post‐Hoc Comparison of the Utility of Sanger Sequencing and Exome Sequencing for the Diagnosis of Heterogeneous Diseases

The advent of massive parallel sequencing is rapidly changing the strategies employed for the genetic diagnosis and research of rare diseases that involve a large number of genes. So far it is not clear whether these approaches perform significantly better than conventional single gene testing as requested by clinicians. The current yield of this traditional diagnostic approach depends on a complex of factors that include gene‐specific phenotype traits, and the relative frequency of the involvement of specific genes. To gauge the impact of the paradigm shift that is occurring in molecular diagnostics, we assessed traditional Sanger‐based sequencing (in 2011) and exome sequencing followed by targeted bioinformatics analysis (in 2012) for five different conditions that are highly heterogeneous, and for which our center provides molecular diagnosis. We find that exome sequencing has a much higher diagnostic yield than Sanger sequencing for deafness, blindness, mitochondrial disease, and movement disorders. For microsatellite‐stable colorectal cancer, this was low under both strategies. Even if all genes that could have been ordered by physicians had been tested, the larger number of genes captured by the exome would still have led to a clearly superior diagnostic yield at a fraction of the cost.