Non-HLA immunogenetic polymorphisms and the risk of complications after allogeneic hemopoietic stem-cell transplantation

BACKGROUND: Existing data indicate that non-human leukocyte antigen (HLA) immunogenetic polymorphisms influence the risk of complications after allogeneic hemopoietic stem-cell transplantation. However, prior studies have been limited by small sample size and limited genotyping. METHODS: We examined 22 polymorphisms in 11 immunoregulatory genes including cytokines, mediators of apoptosis, and host-defense molecules by polymerase chain reaction using sequence-specific primers in 160 related myeloablative transplants. Associations were confirmed in two independent cohorts. RESULTS: An intronic polymorphism in the tumor necrosis factor gene (TNF 488A) was associated with the risk of acute graft-versus-host disease (GVHD) (odds ratio [OR] 16.9), grades II to IV acute GVHD (OR 3.3), chronic GVHD (OR 12.5), and early death posttransplant (OR 3.4). Recipient Fas -670G and donor interleukin (IL)-6 -174G were independent risk factors for acute GVHD. Recipient IL-10 ATA and Fas -670 genotype were independent risk factors for chronic GVHD. Recipient IL-1beta +3953T was associated with hepatic acute GVHD, and Fas -670G was associated with major infection. CONCLUSIONS: These results highlight the potential importance of cytokine and apoptosis gene polymorphisms in stem-cell transplantation, and indicate that non-HLA genotyping may be useful to identify individuals at the highest risk of complications and new targets for therapeutic intervention.     

Preservation of porcine non-heart-beating donor livers by sequential cold storage and warm perfusion

BACKGROUND: Normothermic perfusion has been shown to resuscitate and maintain viability of non-heart-beating donor (NHBD) livers that have undergone significant warm ischemic injury. However, the logistics of clinical organ retrieval are complex, and a period of cold storage before warm preservation would simplify the process. We have investigated the effects of short duration of cold preservation before normothermic preservation on the function of porcine NHBD livers. METHODS: Porcine livers were subjected to 60 minutes of warm ischemia and then assigned to the following groups: group W (n=5), normothermic preservation for 24 hours; and group C (n=4), cold preservation in University of Wisconsin solution for 4 hours followed by normothermic preservation for 20 hours (total preservation time 24 hours). Outcome parameters that were measured included bile production, serum transaminases and hyaluronic acid levels (cellular damage), and base deficit and glucose use (metabolic function). RESULTS: Group W livers had superior bile production, metabolic activity (base deficit and greater glucose use), and less evidence of hepatocellular damage (alanine aminotransferase, aspartate aminotransferase), and sinusoidal endothelial cell dysfunction (hyaluronic acid). Group C livers showed greater necrosis and destruction of architecture on histology. CONCLUSION: Normothermic perfusion failed to resuscitate porcine livers after 60 minutes of warm ischemia and 4 hours of cold preservation. Even a short period of cold ischemia is significantly deleterious to the function of ischemically damaged (NHBD) livers.     

Histomorphometric evaluation of daily and intermittent oral ibandronate in women with postmenopausal osteoporosis: results from the BONE study

The bisphosphonate ibandronate, administered either daily or intermittently with an extended between-dose interval of >2 months, has been shown to reduce significantly the incidence of vertebral fractures, to increase bone mineral density and to reduce levels of biochemical markers of bone turnover in a phase III randomized study in women with postmenopausal osteoporosis (PMO). Bone histomorphometry was performed on a subgroup of women participating in this study in order to assess bone quality and architecture. The patients were randomized to receive one of the following: placebo, continuous oral daily ibandronate (2.5 mg/day) or intermittent oral ibandronate (20 mg every other day for 12 doses every 3 months). Out of the overall study population of 2,946 patients, 110 were randomly assigned to undergo transiliac bone biopsy at either month 22 or month 34 of treatment. The primary safety endpoint was osteoid thickness in trabecular bone, which was measured to exclude treatment-induced bone mineralization defects. Secondary safety endpoints assessed bone volume, bone turnover and micro-architecture. The primary efficacy endpoint was bone mineralizing surface. In all bone biopsy cores, newly formed trabecular bone retained its structure without any signs of woven bone. Marrow fibrosis and signs of cellular toxicity were not observed. Quantitative assessment demonstrated no impairment in mineralization of bone matrix: osteoid thickness tended to be similar or slightly lower in the ibandronate groups versus the placebo group. All secondary safety variables and the bone efficacy parameter were consistent with the production of normal-quality, newly formed bone and a modest reduction in bone turnover with both ibandronate regimens relative to placebo. Long-term treatment with oral ibandronate, even when administered with an extended between-dose interval of >2 months, produces normal-quality, newly formed bone in women with PMO.     

Pseudo-tumours of the urinary tract in patients with spinal cord injury/spina bifida

OBJECTIVE: To raise awareness of pseudo-tumours of urinary tract, as pseudo-tumours represent benign mass lesions simulating malignant neoplasms. Accurate diagnosis helps to avoid unnecessary surgery in spinal cord injury patients. SETTING: Regional Spinal Injuries Centre, Southport, UK CASE REPORTS: Pseudo-tumour of kidney: A 58-year-old man with tetraplegia developed a right perirenal haematoma while taking warfarin; ultrasound and CT scanning showed no evidence of tumour in the right kidney. The haematoma was drained percutaneously. After 8 months, during investigation of a urine infection, ultrasound and CT scan revealed a space-occupying lesion in the mid-pole of the right kidney. CT-guided biopsy showed features suggestive of an organising haematoma; the lesion decreased in size over the next 13 months, thus supporting the diagnosis. Pseudo-tumour of urinary bladder: A frail, 34-year-old woman, who had spina bifida, marked spinal curvature and pelvic tilt, had been managing her neuropathic bladder with pads. She had recurrent vesical calculi and renal calculi. CT scan was performed, as CT would be the better means of evaluating the urinary tract in this patient with severe spinal deformity. CT scan showed a filling defect in the base of the bladder, and ultrasound revealed a sessile space-occupying lesion arising from the left bladder wall posteriorly. Flexible and, later, rigid cystoscopy and biopsy demonstrated necrotic slough and debris but no tumour. Ultrasound scan after 2 weeks showed a similar lesion, but ultrasound-guided biopsy was normal with nothing to explain the ultrasound appearances. A follow-up ultrasound scan about 7 weeks later again showed an echogenic mass, but the echogenic mass was seen to move from the left to the right side of the bladder on turning the patient, always maintaining a dependent position. The echogenic bladder mass thus represented a collection of debris, which had accumulated as a result of chronic retention of urine and physical immobility. CONCLUSION: Recognising the true, non-neoplastic nature of these lesions enabled us to avoid unnecessary surgical procedures in these patients, who were at high risk of surgical complications because of severely compromised cardiac and respiratory function.     

Body-Weight Fluctuation in Collegiate Wrestlers: Implications of the National Collegiate Athletic Association Weight-Certification Program

OBJECTIVE: To determine fluctuations in total body weight of the elite collegiate wrestler during the competitive season. DESIGN AND SETTING: The study period lasted 2 competitive seasons, beginning 1 month before the 1999-2000 and 2000- 2001 competitive seasons and ending 1 month after the National Championships. SUBJECTS: Seventy-eight male subjects (age = 21.3 +/- 1.5 years, height = 154.1 +/- 0.5 cm) from 4 major universities whose teams finished in the top 5 at both the 2000 and 2001 National Collegiate Athletic Association Division I National Wrestling Championships. MEASUREMENTS: Each subject was asked to report to the testing area 24 hours before, 1 hour before, and 24 hours after a competitive wrestling match, and weight was recorded to the nearest 0.1 lb (0.45 kg). Comparisons among the prematch weights, official weigh-ins, and postmatch weights were made using a randomized, 1-group, repeated-measures factorial analysis of covariance with an alpha level of.05. RESULTS: A significant difference (F(2,154) = 229.99, P <.0001) existed in subjects' weights 24 hours (73.93 +/- 11.62 kg) and 1 hour (72.53 +/- 11.66 kg) before a competitive match and 24 hours after (73.65 +/- 13.58 kg) a competitive match. Additionally, we computed 2 t tests to determine the difference among weight changes 24 hours and 1 hour before and 24 hours after a competitive wrestling match. A significant difference was noted between body-weight changes 24 hours and 1 hour before the match (t(77) = 56.21, P <.0001). CONCLUSIONS: Elite collegiate wrestlers, like novice wrestlers, significantly reduce weight immediately before and gain weight after the competition.     

An attachment-based treatment of maltreated children and young people

Repetitive, intrafamilial abuse and neglect leads to a complex array of deficiencies and symptoms that reflect both the traumatic effects of maltreatment on children as well as the effects of their failing to develop a coherent pattern of attachment behaviours toward their caregivers. This article will attempt to describe principles of a psychological treatment for maltreated children and young people who have been placed in foster care and adoptive homes. This treatment, based on attachment theory, provides dyadic interventions that aim to be transforming and integrative. The co-regulation of affect and the co-construction of meaning are central to the treatment process, just as they are central features in attachment security.     

Effect of serum albumin on glycosaminoglycan inhibition of hydroxyapatite formation

The interaction of proteins with hydroxyapatite (HAP), specifically proteoglycans and their spatial arms, glycosaminoglycans (GAGs) in addition to serum proteins, play an important role in regulating biological mineralisation. In this study, seeded HAP growth experiments revealed that inhibition of HAP formation by bovine serum albumin (BSA) was significantly elevated in combination with chondroitin 4-sulphate (C4S) versus BSA with heparin. Data suggest that C4S and BSA adsorb to different calcium sites on the HAP surface. In contrast, complexes of heparin and BSA may adsorb to HAP, thus reducing the rate of inhibition due to steric effects. In addition, the amount of protein bound to HAP growth seed was significantly higher in the presence of heparin versus C4S, confirming this suggestion. Furthermore, the data indicate that a GAG-induced conformational change in BSA occurs, which affects inhibition. This work provides novel information concerning binary molecule modulation of HAP growth.     

A multicentre randomized controlled trial of expectant management versus IVF in women with Fallopian tube patency

BACKGROUND: Although observational studies suggest that IVF is more effective than no treatment for women with Fallopian tube patency, this has not been tested rigorously in a randomized controlled trial (RCT). METHODS: Eligible consenting couples planning their first treatment cycle in five Canadian fertility clinics received either IVF, within 90 days of randomization, or a period of 90 days with no treatment. Random allocation was stratified by female age and sperm quality, and administered using numbered, opaque, sealed envelopes. Follow-up assessed live birth and associated morbidity. RESULTS: Sixty-eight couples were randomized to a first cycle of IVF and 71 couples had 3 months without treatment. The live birth rates were 20/68 (29%) and 1/71 (1%), respectively. The single delivery in the untreated group was of twins, as were six of the 20 IVF deliveries (30%). An average of 2.0 embryos were transferred and no triplet pregnancies resulted. The relative likelihood of delivery after allocation to IVF was 20.9-fold higher than after allocation to no treatment [95% confidence interval (CI) 2.8-155]. The presence of abnormal sperm did not reduce this likelihood. Treating four women (95% CI 3-6) with one cycle of IVF is required to achieve a single additional birth. CONCLUSIONS: This study provides a valid and up-to-date comparison for policy makers and patients as they make choices around IVF, accurately measuring and confirming a major benefit from treatment.