Drug abusers and poisoned patients: a potential source of organs for transplantation?

One of the major constraints to transplantation of solid organs is lack of availability of grafts and any attempt to use all available donors is to be welcomed. We address the possibility of expanding the transplant donor pool by inclusion of more patients who have suffered intoxication with drugs premortem. Particularly important in this context is the exclusion of organ-specific damage, and also infective risk to the potential recipient due to viral causes in the donor.      

The metabolite morphine-6-glucuronide contributes to the analgesia produced by morphine infusion in patients with pain and normal renal function.

Morphine-6-glucuronide is a metabolite of morphine that binds to the opioid receptor and is analgesic in animals and humans. Although accumulation of morphine-6-glucuronide in patients with renal insufficiency has been implicated in morphine toxicity, the contribution of the metabolite to morphine analgesia in patients with normal renal function has not been established. To evaluate this contribution, we repeatedly sampled blood and assessed effects during and after a loading infusion with morphine (mean duration, 168 minutes) in 14 patients with chronic pain, all of whom had normal serum creatinine levels. Plasma concentrations of morphine and morphine-6-glucuronide were assayed by use of high performance liquid chromatography with electrochemical detection. Patients were divided into three groups on the basis of the molar concentration ratio of morphine-6-glucuronide:morphine from the start of the infusion until 240 minutes later: Group 1 (n = 5) had a mean ratio greater than or equal to 0.7:1; group 2 (n = 4) had a mean ratio less than 0.7:1 but greater than or equal to 0.4:1; and group 3 (n = 5) had a mean ratio less than 0.4:1. Time-effect plots revealed that average and peak relief were greater in group 1 than group 2 and greater in group 2 than group 3. For all patients, mean morphine-6-glucuronide:morphine ratio throughout the study was significantly correlated with mean pain relief (r = 0.611, p less than 0.02). These data suggest that morphine-6-glucuronide contributes to morphine analgesia in patients with normal renal function. The role of the metabolite should be considered when morphine is used clinically.     

Accurate quantitation of the low number of white cells in white cell- depleted blood components

A simple method of accurate quantification of low concentrations of white cells (WBCs) in WBC-depleted blood components was developed by using propidium iodide (PI) to stain the nuclei of WBCs. The method was validated by correlating the PI-determined WBC concentrations with those determined with Coulter S-plus IV counter in units of packed red cells (PRBCs) or random-donor platelets (RDPs). The correlations were linear and had coefficients of 0.99. The sensitivity of PI staining permitted the detection of concentrations of WBCs as low as 1 cell per microL of RDPs or 11 cells per microL of PRBCs. Therefore, PI staining will be useful in investigating the role of transfused WBC-depleted blood components in the prevention of primary alloimmunization to HLA antigens, as well in evaluating various new procedures with high efficiency in depleting WBCs from blood components.     

Resistance to activated protein C and factor V Leiden

Over the last four years, there has been an explosion of knowledge about APCr and factor V Leiden. However, there remain a considerable number of difficult clinical areas in which there are no clear answers. Undoubtedly, factor V Leiden is commonly found in association with venous thromboembolic disease in whatever manifestation, but equally it has an unusually high frequency in the general population. Only a small proportion of those that carry the mutation develop a thrombosis. It is estimated that only 6% of those that carry the mutation will develop a thrombosis over a 30-year period, whilst for antithrombin, Protein C or Protein S deficiency, this figure is nearer 60%. Particular areas of difficulty remain in relation to the use of the combined OCP and in the management of the asymptomatic carrier of the mutation in pregnancy. Although the scientific basis of APCr and factor V Leiden is well established, its natural history remains relatively poorly understood, probably as a consequence of its relative novelty. Despite the plethora of new data that have appeared, there remains much to be learnt about factor V Leiden and the APCr phenotype.      

Transvaginal ultrasonography in the diagnosis and treatment of infertility

The use of transvaginal sonography (TVS) in the management of infertility is gaining increasing popularity. The improved resolution and better tissue textural differentiation afforded by TVS makes this technique useful in monitoring ovarian follicular growth, ovulation, and corpus luteum formation, and in evaluating the normal anatomy of the uterus and the cervix and their cyclic response to ovarian steroids. Adnexal and cul-de-sac abnormalities related to infertility can also be identified. TVS-guided procedures can be accurately and safely performed; transvaginal follicular aspiration, gamete or embryo transfer to the Fallopian tube, and fetal reduction are just a few of the procedures recently introduced to reproductive medicine.     

Chronic active hepatitis associated with vitiligo, nail dystrophy, alopecia and a new variant of LKM antibodies

In this report we describe the case of a 7-year-old boy, suffering from autoimmune-type chronic active hepatitis (AI-CAH) associated with vitiligo, nail dystrophy, alopecia areata and a variant of liver kidney microsomal (LKM) autoantibodies. This patient's antibodies are different from LKM-1 which are directed against cytochrome P450 db1. They react predominantly with perivenous hepatocytes in contrast to LKM-1 antibodies which homogeneously stain the whole liver lobule in immunofluorescence. In Western blot analysis this LKM variant reacts with a liver microsomal protein of approx. 50 kDa, but not with recombinant LKM-1 (cytochrome P450 db1) antigen. Immunosuppressive treatment led to a normalization of liver histology after 1 year and a significant improvement of vitiligo and alopecia areata. In summary, a case of autoimmune-type chronic active hepatitis is presented which is associated with a new variant of LKM antibodies reacting with a 50 kDa microsomal protein different from cytochrome P450 db1. Furthermore, this patient suffers from extrahepatic syndromes (alopecia, nail dystrophy) that have not been described previously in LKM antibody-positive chronic active hepatitis.     

An aggressive subtype of B-CLL is characterized by strong CD44 expression and lack of CD11c

In a retrospective study based on 107 B-CLL patients, the expression of the adhesion molecules CD44, CD11a, CD11b, CD11c, CD18, CD25 and CD54 was analysed in bone marrow cryostat sections by immunohistochemistry. CD44 expression clearly identified two subgroups of B-CLL patients with different clinical course. In particular, CD44-positive patients presented with advanced disease, more often displayed a diffuse pattern of bone marrow infiltration, and had a worse prognosis. 33/61 patients positive for CD44 died within the observation period compared to 7/46 patients negative for CD44 ( P  = 0.0012). Multivariate analysis emphasized the independent prognostic value of CD44 expression for overall survival ( P  = 0.022). In contrast, patients positive for CD11c showed a longer survival, with 9/40 patients dying within the observation period compared to 31/67 negative for CD11c ( P  = 0.0013). Patients lacking CD11c were in advanced Rai and Binet stage. Multivariate analysis confirmed CD11c as a relevant independent prognostic marker ( P  = 0.033). Moreover, CD11c was able to separate patients with significantly different prognosis in the subgroup of CD44-positive cases. 4/18 patients positive for CD44 and CD11c died before median survival time was reached. Patients positive for CD44 but negative for CD11c had an adverse prognosis: 29/43 patients died, median survival time was 33.4 months.   Our results indicate that CD44 positivity and CD11c negativity are associated with more advanced disease and worse prognosis in B-CLL and suggest CD44-positive/CD11c-negative cases represent a more aggressive form of the disease.