Clinical validation of routine antenatal anti-D prophylaxis questions the modelling predictions adopted by NICE for Rhesus D sensitisation rates: results of a longitudinal study

OBJECTIVE: To compare the rates of Rh(D) sensitisations with a policy of restricted routine antenatal anti-D prophylaxis (first pregnancy only) with the rates predicted with universal routine antenatal anti-D prophylaxis (all pregnancies). STUDY DESIGN: A retrospective longitudinal observational study involving 15,500 confinements in Rhesus D negative (Rh(D)-ve) women between 1990 and 2003 in a single health district was conducted. All Rh(D) sensitised pregnancies were identified and evidence for routine antenatal anti-D prophylaxis administration during the first pregnancy was investigated. The rate of Rh(D) sensitisations following a policy of restricted prophylaxis was compared with that predicted with mathematical modelling following universal prophylaxis. RESULTS: There were 50 newly sensitised and 37 previously sensitised pregnancies among 15,596 Rh(D)-ve women. For the calculated 13,575 Rh(D)-ve women whose first confinement was in Oxford and who were eligible for restricted prophylaxis, there were 30 new and 26 previously sensitised pregnancies. Of these 30 new sensitisations, 10 were nulliparae, 12 parity 1, and eight parity 2 or greater (third or later continuing pregnancy); only one of these latter eight women had received routine prophylaxis, four had delivered their first baby before the programme was introduced, and in three documentary evidence could not be confirmed that prophylaxis had been given. There was no difference between a policy of restricted and universal routine antenatal anti-D prophylaxis in the sensitisation rates for women during their third or subsequent pregnancy. CONCLUSIONS: This study has shown that restricted routine antenatal prophylaxis provides continuing protection for subsequent pregnancies although the mechanism for this is unclear. These results challenge the wisdom and expense of a policy of universal prophylaxis and prompt a need for further similar analyses to test the appropriateness of the NICE guideline.     

A new heparin fragment decreases liver ischemia-reperfusion injury

<正>To the Editor:Ischemia-reperfusion injury following surgery and transplantation can lead to irreversible multiorgan failure.Intracellular calcium overload is associated to cellular death during ischemiareperfusion.A recently discovered heparin fragment (HF),trisulfated disaccharide (TD),that acts on sodium-calcium exchanger(NCX) decreasing intracellular Ca²⁺,showed effectiveness on protecting hepatocytes from ischemia-reperfusion injury [1],     

Use of monoclonal antibodies to identify cerebrospinal fluid lymphoblasts in children with acute lymphoblastic leukemia

The identification of small numbers of leukemic cells in the cerebrospinal fluid (CSF) presents a diagnostic problem in the treatment of children with acute lymphoblastic leukemia (ALL). We adapted a latex sphere rosetting technique to allow us to identify simultaneously cell surface markers and cell morphology in 199 CSF samples from 34 patients and 14 control subjects. In patients without leukemic meningitis, the majority of CSF lymphocytes (69%) were found to be mature T cells positive for OKT11. A much smaller number of cells (8%) were found to be B cells positive for la. In these children, only 3% of CSF lymphoid cells expressed the common acute lymphoblastic leukemia antigen (CALLA). Similar results were found in the control subjects. By contrast, 28 CSF samples from nine children with varying numbers of CSF lymphoblasts had much greater proportions of CALLA- and la-positive CSF cells (24% to 96%). Leukemic meningitis was present in one of these patients and later developed in four others. However, three patients with small numbers of lymphoblasts present but with low proportions of CALLA-positive CSF cells (less than 5%) subsequently had normal CSF examinations. We found the use of this rosetting technique valuable in providing information complementary to that obtained from cell morphology alone about the possible malignant nature of small numbers of lymphoblast-like CSF cells seen on cytocentrifuge preparations in children with ALL.     

Transplantation of cryopreserved osteochondral Dowel allografts for repair of focal articular defects in an ovine model.

The purpose of this study was to test whether successful cryopreservation of osteochondral tissue is possible and whether, with the appropriate surgical procedure, it can be used for the successful repair of focal articular defects within joints. Fresh (nonfrozen) and snap-frozen (plunged in liquid nitrogen and thawed in a water bath at 37 degrees C, repeated three times) autografts were used as positive and negative controls, respectively. Snap-frozen, frozen (fresh tissue placed in a freezer at -80 degrees C), and cryopreserved (immersed in 10% dimethyl sulfoxide for 30 minutes and then frozen at 1 degrees C/min to -80 degrees C) allografts were transplanted into the knees of adult sheep. Outcomes were evaluated 3, 6, and 12 months after transplantation. The morphological, histological, biochemical, and biomechanical behaviors and characteristics of the graft cartilage, the host cartilage adjacent to the grafts, and the opposing tibial cartilage were assessed. Freezing protocols that yielded poor chondrocyte recovery after thawing (frozen and snap-frozen) resulted in poor overall graft outcome. The cryopreservation protocol, however, resulted in intermediate recovery (50%) of chondrocytes and in intermediate overall graft outcome compared with fresh autografts. The membrane integrity of the allograft chondrocytes immediately following cryopreservation was identified as the most reliable predictor of long-term outcome of the graft. Further improvements in cryopreservation technique may lead to an effective method of banking osteochondral tissue for successful transplantation for the repair of focal defects and larger joint reconstructions.     

Coil occlusion of the parent artery for treatment of symptomatic peripheral intracranial aneurysms

BACKGROUND AND PURPOSE: Peripheral intracranial aneurysms can be difficult to treat with traditional surgical or embolization techniques that spare the parent vessel. We report the results of our use of coil occlusion of the parent vessel for the treatment of nine peripheral intracranial aneurysms. METHODS: During approximately a 4-year period, nine patients (six men and three women, 27 to 68 years old; average age, 42 years) presented to our institution with peripheral intracranial aneurysms. The aneurysms were located on branches of the right posterior inferior cerebellar artery (n = 2), the right superior cerebellar artery (n = 1), the right anterior inferior cerebellar artery (n = 1), the right posterior cerebral artery (n = 3), the left middle cerebral artery (n = 1), and the left anterior cerebral artery (n = 1). Parent vessel occlusion was performed using microcoils after test injection with amobarbital (Amytal) in eight of the nine cases (one patient was comatose and could not be tested before occlusion). RESULTS: Angiography immediately after the procedure showed aneurysmal occlusion in every patient. Follow-up arteriography, performed in six patients 2 to 12 months after treatment, documented continued aneurysmal occlusion in every case. Three patients exhibited mild, nondisabling neurologic deficits after coil placement; the rest had no new deficits, although one patient was severely disabled from the initial hemorrhage and one patient died of an unrelated cause. CONCLUSION: Our results lend support to the use of parent vessel occlusion for peripheral aneurysms that are difficult to treat surgically or that are not amenable to intra-aneurysmal coil placement.     

Ventral hernia repair: a study of current practice

Ventral wall hernias are common; despite this, there are no guidelines on the best surgical management. The aim of this study was to examine the types of repair in use for abdominal wall hernias in the West of Scotland over a 3-month period. Data were gathered on 120 patients. There were 60 incisional, 32 umbilical, and 28 epigastric hernias. The main indication for repair was pain (78%), while 12 patients (10%), presented acutely with incarceration or strangulation. The most common method of repair was sutured (55%), followed by mesh (29%) and Mayo repair (16%). There was no correlation between use of mesh and hernia size or whether repair was for a recurrent hernia. Surgical practice varies widely in the repair of ventral wall hernias. Clinical trials are required to establish the best method of repair for this common condition. Electronic Publication     

Thyroid-stimulating hormone restores bone volume, microarchitecture, and strength in aged ovariectomized rats.

We show the systemic administration of low levels of TSH increases bone volume and improves bone microarchitecture and strength in aged OVX rats. TSH's actions are mediated by its inhibitory effects on RANKL-induced osteoclast formation and bone resorption coupled with stimulatory effects on osteoblast differentiation and bone formation, suggesting TSH directly affects bone remodeling in vivo. INTRODUCTION: Thyroid-stimulating hormone (TSH) receptor haploinsufficient mice with normal circulating thyroid hormone levels have reduced bone mass, suggesting that TSH directly affects bone remodeling. We examined whether systemic TSH administration restored bone volume in aged ovariectomized (OVX) rats and influenced osteoclast formation and osteoblast differentiation in vitro. MATERIALS AND METHODS: Sprague-Dawley rats were OVX at 6 months, and TSH therapy was started immediately after surgery (prevention mode; n = 80) or 7 mo later (restoration mode; n = 152). Hind limbs and lumbar spine BMD was measured at 2- or 4-wk intervals in vivo and ex vivo on termination at 8-16 wk. Long bones were subjected to microCT, histomorphometric, and biomechanical analyses. The direct effect of TSH was examined in osteoclast and osteoblast progenitor cultures and established rat osteosarcoma-derived osteoblastic cells. Data were analyzed by ANOVA Dunnett test. RESULTS: In the prevention mode, low doses (0.1 and 0.3 microg) of native rat TSH prevented the progressive bone loss, and importantly, did not increase serum triiodothyroxine (T3) and thyroxine (T4) levels in aged OVX rats. In restoration mode, animals receiving 0.1 and 0.3 microg TSH had increased BMD (10-11%), trabecular bone volume (100-130%), trabecular number (25-40%), trabecular thickness (45-60%), cortical thickness (5-16%), mineral apposition and bone formation rate (200-300%), and enhanced mechanical strength of the femur (51-60%) compared with control OVX rats. In vitro studies suggest that TSH's action is mediated by its inhibitory effects on RANKL-induced osteoclast formation, as shown in hematopoietic stem cells cultivated from TSH-treated OVX rats. TSH also stimulates osteoblast differentiation, as shown by effects on alkaline phosphatase activity, osteocalcin expression, and mineralization rate. CONCLUSIONS: These results show for the first time that systemically administered TSH prevents bone loss and restores bone mass in aged OVX rats through both antiresorptive and anabolic effects on bone remodeling.     

Periprosthetic Tissue Reaction Independent of LTT Result and Implanted Materials in Total Knee Arthroplasty

BackgroundAn allergic reaction may rarely cause a painful or stiff total knee arthroplasty (TKA). However, no consensus diagnostic criteria for TKA immune failure exist. Lymphocyte transformation testing (LTT) measures immune sensitivity to various materials, but its role in diagnosing an allergic reaction to a TKA has not been established. This study compares TKA periprosthetic tissues in a) LTT-positive versus -negative patients and b) patients with conventional CoCrNi versus hypoallergenic implants.MethodsPeriprosthetic tissues from 26 revision cases of well-fixed, aseptic, but painful or stiff TKAs were analyzed. Twelve patients LTT positive for nickel (Ni) were matched as a cohort to 6 LTT-negative patients. In 4 patients LTT positive for Ni, tissue from first revision of CoCrNi implants was compared with tissue from subsequent revision of hypoallergenic implants. Histology was evaluated using the aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) score.ResultsNo correlation was found between LTT and any ALVAL score component. The mean total ALVAL score was 3.8 ± 1.5 for LTT-negative patients and 3.3 ± 1.2 for LTT-positive patients (P = .44). The mean total ALVAL score at revision of CoCrNi implants was 3.0 ± 1.8 compared with 5.8 ± 0.5 at rerevision of hypoallergenic implants (P = .053).ConclusionPeriprosthetic TKA tissue reactions were indistinguishable between LTT-positive and -negative patients. LTT does not predict the periprosthetic tissue response. ALVAL scores of hypoallergenic revision implant tissue trended higher than primary CoCrNi implant tissue. A positive LTT may not indicate that a periprosthetic immune reaction is the cause of pain and stiffness after TKA.Level of Evidence3, retrospective cohort study.