HLA antibody-incompatible kidney transplantation between jehovah's witnesses--a case report.

Desensitization before HLA antibody-incompatible (HLAi) transplantation involves nonspecific apheresis of HLA antibodies. Clotting factors and albumin are also removed and have to be replaced. This makes transplantation difficult because it increases the risk of bleeding. Such risk is further compounded when certain blood products are refused on religious grounds. We present a case of successful HLAi transplantation in a Jehovah's Witness across a positive-flow cytometric HLA crossmatch from a live donor who was also a Jehovah's Witness. This was achieved by giving rituximab 1 month before transplantation and starting prednisolone, tacrolimus, and mycophenolate mofetil 10 days before surgery. In preparation, the patient also underwent 4 sessions of double-filtration plasma exchange each followed by low-dose intravenous immunoglobulin. The night before transplantation, the fibrinogen was low, requiring 2 pools of cryoprecipitate. The organ was retrieved through laparoscopic hand-assisted retroperitoneoscopic nephrectomy and transplanted into the recipient with no complications. In addition, the patient received basiliximab during surgery. Sixteen months after transplantation the serum creatinine was 70 µmol/L (0.79 mg/dL) and there were no rejection episodes. To our knowledge this is the world's first live-related kidney transplant across the HLAi barrier between 2 Jehovah's Witnesses. This case may allow further HLAi transplants to be carried out in Jehovah's Witnesses in the future around the world.

A successful live donor kidney transplantation after large angiomyolipoma excision.

INTRODUCTION: Angiomyolipoma is the most common benign neoplasm of the kidney. Successful transplantation of an AML affected kidney has been reported. However it is still often seen as a contraindication to transplantation. PRESENTATION OF CASE: A 47-year-old female underwent assessment for a direct specified kidney donation to her husband who had end stage renal failure, due to adult polycystic kidney disease. Routine pre-operative CT angiography demonstrated a large 6cm×4cm AML arising from the upper pole of the right kidney. Right-side hand assisted retro-peritoneoscopic live donor nephrectomy with bench tumour excision was subsequently performed. Recipient implantation was unremarkable with no haemorrhage. DISCUSSION: Histology confirmed a 7cm AML. At 36 months follow up, the recipient's serum creatinine was 158µmol/l and eGFR 40ml/min without the need for dialysis at any stage. CONCLUSION: AML should not be a contraindication for specified live kidney donation, despite a size of 7cm.

Mechanical complications of long-term Tesio catheters.

Vascular access catheters such as Tesio-Caths are preferentially inserted in the internal jugular vein and serve as access for hemodialysis. Complications related to the removal of these types of lines are uncommon. We report four patients in whom the tip of the Tesio-Cath broke and was left stuck in the superior vena cava. Although there is no defined limit to the maximum length of stay of vascular access catheters for dialysis, the possibility of catheter entrapment should be considered. It remains to be determined whether removing Tesio-Caths every 16- 18 months is beneficial in avoiding this complication.

Risk-adjusted prediction of operative mortality in oesophagogastric surgery with O-POSSUM.

INTRODUCTION: The present study was designed to develop a dedicated oesophagogastric model for the prediction of risk-adjusted postoperative mortality in upper gastrointestinal surgery (O-POSSUM). METHODS: Using 1042 patients undergoing oesophageal (n = 538) or gastric (n = 504) surgery between 1994 and 2000 the Portsmouth predictor equation for mortality (P-POSSUM) scoring system was compared with a standard logistic regression O-POSSUM model and a multilevel O-POSSUM model using the following independent factors: age, physiological status, mode of surgery, type of surgery and histological stage. RESULTS: The overall mortality rate was 12.0 per cent (elective mortality rate 9.4 per cent and emergency mortality rate 26.9 per cent). P-POSSUM overpredicted mortality (14.5 per cent), particularly in the elective group of patients. The multilevel model offered higher discrimination than the single-level O-POSSUM and P-POSSUM models (area under receiver-operator characteristic curve 79.7 versus 74.6 and 74.3 per cent). When observed to expected outcomes were evaluated, the multilevel O-POSSUM model was found to offer better calibration (Hosmer-Lemeshow chi(2) statistic 10.15 versus 10.52 and 28.80). CONCLUSION: The multilevel O-POSSUM model provided an accurate risk-adjusted prediction of death from oesophageal and gastric surgery for individual patients. In conjunction with a multidisciplinary approach to patient management, the model may be used in everyday practice for perioperative counselling of patients and their carers.

Evaluation of POSSUM and P-POSSUM scoring systems in patients undergoing colorectal surgery.

BACKGROUND: The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) and Portsmouth POSSUM (P-POSSUM) equations were derived from a heterogeneous general surgical population and have been used successfully as audit tools to provide risk-adjusted operative mortality rates. Their applicability to high-risk emergency colorectal operations has not been established. METHODS: POSSUM variables were recorded for 1017 patients undergoing major elective (n = 804) or emergency (n = 213) colorectal surgery in ten hospitals. Subgroup analysis was performed to investigate the predictive capability of POSSUM and P-POSSUM in emergency and elective surgery and in patients in different age groups. RESULTS: The overall operative mortality rate was 7.5 per cent (POSSUM-estimated mortality rate 8.2 per cent; P-POSSUM-estimated mortality rate 7.1 per cent). In-hospital deaths increased exponentially with age. Both scoring systems overpredicted mortality in young patients and underpredicted mortality in the elderly (P < 0.001). Death was underpredicted by both systems for emergency cases, significantly so at a simulated emergency caseload of 47.9 per cent (P < 0.05). CONCLUSION: There is a lack of calibration of POSSUM and P-POSSUM systems at the extremes of age and high emergency workload. This has important implication in clinical practice, as consultants with a high emergency workload may seem to underperform when these scoring systems are applied. Recalibration or remodelling strategies may facilitate the application of POSSUM-based systems in colorectal surgery.

Ventral neurogenesis and the neuron-glial switch.

In the developing spinal cord, neuroepithelial precursors at different positions along the dorsal-ventral axis generate distinct neuronal and glial subtypes. For example, one group of ventral precursors generates neurons followed by oligodendrocytes. A spate of recent articles, including several in this issue of Neuron, are devoted to the mechanisms governing neuronal and glial subtype specification in the ventral cord. We review these studies and discuss the nature of the ventral neuron-oligodendrocyte switch.

Hedgehog-dependent oligodendrocyte lineage specification in the telencephalon.

In the caudal neural tube, oligodendrocyte progenitors (OLPs) originate in the ventral neuroepithelium under the influence of Sonic hedgehog (SHH), then migrate throughout the spinal cord and brainstem before differentiating into myelin-forming cells. We present evidence that oligodendrogenesis in the anterior neural tube follows a similar pattern. We show that OLPs in the embryonic mouse forebrain express platelet-derived growth factor alpha-receptors (PDGFRA), as they do in more caudal regions. They first appear within a region of anterior hypothalamic neuroepithelium that co-expresses mRNA encoding SHH, its receptor PTC1 (PTCH) and the transcription factors OLIG1, OLIG2 and SOX10. Pdgfra-positive progenitors later spread through the forebrain into areas where Shh is not expressed, including the cerebral cortex. Cyclopamine inhibited OLP development in cultures of mouse basal forebrain, suggesting that hedgehog (HH) signalling is obligatory for oligodendrogenesis in the ventral telencephalon. Moreover, Pdgfra-positive progenitors did not appear on schedule in the ventral forebrains of Nkx2.1 null mice, which lack the telencephalic domain of Shh expression. However, OLPs did develop in cultures of Nkx2.1(-/-) basal forebrain and this was blocked by cyclopamine. OLPs also developed in neocortical cultures, even though Shh transcripts could not be detected in the embryonic cortex. Here, too, the appearance of OLPs was suppressed by cyclopamine. In keeping with these findings, we detected mRNA encoding SHH and Indian hedgehog (IHH) in both Nkx2.1(-/-) basal forebrain cultures and neocortical cultures. Overall, the data are consistent with the idea that OLPs in the telencephalon, possibly even some of those in the cortex, develop under the influence of SHH in the ventral forebrain.

Oligodendrocyte development in the spinal cord and telencephalon: common themes and new perspectives.

There are clear parallels between oligodendrocyte development in the spinal cord and forebrain. However, there is new evidence that in both of these regions oligodendrocyte lineage development may be more complex than we earlier thought. This stems from the recent identification of three new transcription factor genes, Olig1, Olig2 and Sox10, that are expressed from the early stages of oligodendrocyte lineage development. In this article, we highlight the common themes underlying specification and early development of oligodendrocytes in the spinal cord and telencephalon. Then, we discuss recent studies of Sox10 and the Olig genes and their implications for oligodendrocyte specification. We conclude that although the mechanisms of oligodendrogenesis appear to be fundamentally similar at different rostro-caudal levels of the neuraxis, there are still many unanswered questions about the details of oligodendrocyte specification.

The role of mini-fragment screw fixation in volar dislocations of the proximal interphalangeal joint.

Palmar fracture-dislocations of the proximal interphalangeal (PIP) joint are uncommon injuries, which can be associated with long-term complications if sub-optimally treated. We report two cases of palmar fracture-dislocations of the PIP joint treated by open reduction and internal fixation using a single mini-fragment screw. The long term results of hand and finger function were excellent.

Characterisation, chromosomal localisation and expression of the mouse Kid3 gene.

Kid1 encodes a transcriptional repressor implicated in the differentiation of renal epithelial cells. Here we report the characterisation of Kid3, a novel mouse gene related to Kid1. Kid3 encodes a C2H2 zinc finger protein with an N-terminal KRAB transcriptional repression domain. It maps to chromosome 11, adjacent to Kid1 and another related gene Kid2. Northern analysis shows that Kid3 is highly expressed in embryonic and adult brain, with lower levels in adult and embryonic (E16.5) kidney, gut, lung and heart. Expression of Kid3 in the kidney is developmentally regulated and suggests a role for Kid3 in the early stages of nephrogenesis.

Palmar dislocation of the proximal interphalangeal joint--an injury not to be missed.

Palmar dislocations of the proximal interphalangeal (PIP) joint are associated with long term complications if suboptimally treated. Six cases of palmar dislocation of the PIP joint are presented and a systematic approach in the diagnosis and management of such injuries in the accident and emergency department is described.

Characterization of the mouse Kid1 gene and identification of a highly related gene, Kid2.

Kid1 encodes a zinc finger protein that has been implicated in renal cell differentiation. Levels of Kid1 mRNA correlate with maturation of kidney tubule epithelia in rat post-natal kidney development and during kidney regeneration following injury. KID1 is a putative transcriptional repressor, containing a KRAB domain at its amino terminus that mediates transcriptional repression in transient cell transfection assays when fused to a heterologous DNA-binding domain. In this paper, we describe the isolation and characterization of the mouse homologue of Kid1 and the identification of a novel highly related mouse gene, Kid2, Kid1 and Kid2 are tightly linked on mouse chromosome 11 and show conservation across mammals. Both genes are expressed predominantly in the mouse adult kidney and brain, but transcripts are also detected in embryonic brain, kidney, gut and lung, suggesting an additional role for these genes during mouse development.

Polymerase chain reaction fails to incriminate exogenous retroviruses HTLV-I and HIV-1 in rheumatological diseases although a minority of sera cross react with retroviral antigens.

OBJECTIVES: To investigate the presence of antibodies to HTLV and HIV retroviral antigens in the rheumatological diseases rheumatoid arthritis (RA), polymyositis/dermatomyositis (PM/DM), primary Sjögren's syndrome (pSS), and systemic lupus erythematosus (SLE), and to use polymerase chain reaction (PCR) to seek these exogenous retroviruses in proviral form in cellular DNA from these patients. METHODS: Thirty patients with active RA, 13 with PM, 14 with pSS and five with SLE were recruited and their sera tested for antibodies to HTLV-I in enzyme linked immunosorbent assay (ELISA) and Western blot analysis. Seropositivity to HIV-1 was also sought. DNA was extracted from peripheral blood lymphocytes, synovial tissue and muscle biopsies and tested by polymerase chain reaction using consensus primers for HTLV-I and HIV-1. RESULTS: In HTLV-I ELISA, nine rheumatological sera (4/30 RA, 3/13 PM/DM and 2/5 SLE patients) were considered positive; 14 from pSS patients and 30 from normal subjects were negative. In a control group which included osteoarthritis, Crohn's disease and bacterial endocarditis patients, only two of 80 proved positive in this system. Validation of these sera by Western blotting generally revealed weak reactivity against a variety of HTLV-I antigens. PCR of genomic DNA derived from patients' peripheral blood mononuclear cells did not reveal the presence of HTLV-I and HIV-1 target sequences. CONCLUSIONS: This study shows that PCR precludes HTLV-I and HIV-1 infection as causative agents in these rheumatological diseases although a minority of patients possess antibodies that are weakly cross-reactive with retroviral antigens.

Rectal thermoluminescent dosimeter measurements using the MicroSelectron High Dose Rate afterloader in postoperative intravaginal radiation cases.

PURPOSE: The purpose of this study is twofold: First, to measure the dose distribution along the anterior and posterior rectal wall, compare them to the prescribed dose and establish the rectal length receiving the maximum dose. Second, to carry out in-phantom dose measurements in order to confirm that the dose planned is in fact the dose delivered. METHODS AND MATERIALS: The dose distribution along the anterior and posterior rectal wall was measured for a group of 25 Gynecologic cases treated with a vaginal cylinder, using the MicroSelectron High Dose Rate system. The method of measurement employed flexible vinyl rectal probes (1 or 2 cm diameter). Two fine plastic tubes, each containing 15 Thermo Luminescent Dosimeters rods, were attached along the probe on opposite sides to measure the anterior and posterior rectal wall dose distributions. RESULTS: The dose distribution exhibited a sharp peak covering a rectal length from one to two centimeters. The peak doses for the anterior rectal wall ranged from 60% to 110% of prescribed dose. In-phantom measurements used layers of phantom material that contained a special source tube for the Iridium-192 source as well as Thermoluminescent Dosimeter tube(s) positioned at 1 cm distance from the source tube. The afterloader was programmed to deliver 300 cGy at 1 cm along its treatment length. CONCLUSION: The Thermo Luminescent Dosimeters measurements showed good agreement with the doses expected on the basis of the treatment plan.

Transverse axial film tomography with a therapy simulator.

A tomographic attachment was designed and developed that attaches to our existing simulator. The film tomograms obtained with the aid of this device exhibit very low geometrical distortion and good contrast and resolution for the objects used in this investigation. In addition, our results to date show that adjacent areas with densities differing by as little as 5% can be distinguished on film.