Antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin antibodies in women with recurrent pregnancy loss, fertile controls, and antiphospholipid syndrome

OBJECTIVE: To determine whether antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin are associated with recurrent pregnancy loss. METHODS: Sera from three groups of women were studied: 1) 147 women with recurrent pregnancy loss but no clinical signs or symptoms of autoimmune disease who tested negative for lupus anticoagulant and medium-to-high levels of immunoglobulin G anticardiolipin antibodies; 2) 104 healthy, fertile controls of similar age and gravidity; and 3) 43 women with well-characterized antiphospholipid syndrome. Serum antibody binding against six phospholipids (cardiolipin, phosphatidic acid, phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol) was determined using enzyme-linked immunoassays, and results were normalized using an anticardiolipin standard. RESULTS: Twenty-six (18%) women with recurrent pregnancy loss and nine (9%) controls tested positive (above the 99th percentile) for antiphospholipid antibodies. Sera from five (3.4%) women with recurrent pregnancy loss and four (3.8%) controls demonstrated binding to phospholipid antigens other than cardiolipin. In contrast, binding to phospholipid antigens was demonstrated in sera from more than 90% of women with antiphospholipid syndrome. Among women testing positive for antiphospholipid antibodies, the median positive value for women in the antiphospholipid syndrome group was significantly higher than for those with recurrent pregnancy loss or normal fertile controls. CONCLUSIONS: Women with recurrent pregnancy loss are no more likely than fertile controls to have elevated levels of antiphospholipid antibodies once lupus anticoagulant, anticardiolipin, and an obvious clinical history of autoimmune disease have been excluded. Testing for antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin is not clinically useful in the evaluation of recurrent pregnancy loss.     

Randomised comparison of subcutaneous heparin, intravenous heparin, and aspirin in unstable angina. Studio Epoorine Sottocutanea nell'Angina Instobile (SESAIR) Refrattorie Group

Intravenous heparin has been used in the control of myocardial ischaemia in patients with unstable angina. We set out to assess the efficacy of subcutaneous heparin in reducing myocardial ischaemia in patients with unstable angina. 343 of 399 patients with unstable angina were monitored for 24 h and 108 were refractory to conventional antianginal treatment and were entered into a randomised multicentre trial. 37 patients were assigned to heparin infusion (partial thromboplastin time 1.5-2 times baseline), 35 to subcutaneous heparin (adjusted dose with partial thromboplastin time 1.5-2 times baseline), and 36 to aspirin (325 mg daily). All had additional conventional antianginal therapy. After the run-in patients were monitored for 3 days. The primary endpoint was reduced myocardial ischaemia assessed by the number of anginal attacks, silent ischaemic episodes, and duration of ischaemia per day. At 1 week and 1 month we accounted for anginal attacks and other clinical events (myocardial infarction, revascularisation procedures, and death). Aspirin did not significantly affect the incidence of myocardial ischaemia. On the first 3 days, infused and subcutaneous heparin significantly decreased the frequency of angina (on average by 91% and 86%, respectively), episodes of silent ischaemia (by 56% and 46%), and the overall duration of ischaemia (66% and 61%) versus run-in day and aspirin (p < 0.001 for all variables). The favourable effects of heparin therapy remained evident during follow-up. Only minor bleeding complications occurred. Subcutaneous heparin is effective in the control of myocardial ischaemia in patients with unstable angina.     

Magnesium and calcium level in blood serum of pregnant women with pregnancy threatening miscarriage

Concentration of magnesium and calcium was determined in the blood serum of 43 women with pregnancy threatening miscarriage and 32 ones with normal uterine pregnancy in the time interval from 6th to 22nd week. I spite of considerable oscillations in magnesium concentration, particularly in the group of threatened pregnancies as compared with the normal ones, the differences were not significant. Neither were there found any significant differences in calcium concentration between the populations tested.     

The syndrome of thrombosis, thrombocytopenia, and recurrent spontaneous abortions associated with antiphospholipid antibodies: Hughes syndrome

aPL-associated thrombosis (Hughes syndrome) is widely recognized as a major cause of organ damage in autoimmune diseases. Beginning with the first symposium in 1984, international aPL symposia have facilitated research on aPL antibodies, and the clinical standardization of aPL tests. It is hoped that the present symposium will continue this tradition, because much remains to be learnt about the origin and pathogenicity of aPL antibodies. In addition, new insights are needed for more effective therapies to be developed.     

Randomised controlled trial of a general practice programme of home based exercise to prevent falls in elderly women

OBJECTIVE: To assess the effectiveness of a home exercise programme of strength and balance retraining exercises in reducing falls and injuries in elderly women. DESIGN: Randomised controlled trial of an individually tailored programme of physical therapy in the home (exercise group, n = 116) compared with the usual care and an equal number of social visits (control group, n = 117). SETTING: 17 general practices in Dunedin, New Zealand. SUBJECTS: Women aged 80 years and older living in the community and registered with a general practice in Dunedin. MAIN OUTCOME MEASURES: Number of falls and injuries related to falls and time between falls during one year of follow up; changes in muscle strength and balance measures after six months. RESULTS: After one year there were 152 falls in the control group and 88 falls in the exercise group. The mean (SD) rate of falls was lower in the exercise than the control group (0.87 (1.29) v 1.34 (1.93) falls per year respectively; difference 0.47; 95% confidence interval 0.04 to 0.90). The relative hazard for the first four falls in the exercise group compared with the control group was 0.68 (0.52 to 0.90). The relative hazard for a first fall with injury in the exercise group compared with the control group was 0.61 (0.39 to 0.97). After six months, balance had improved in the exercise group (difference between groups in change in balance score 0.43 (0.21 to 0.65). CONCLUSIONS: An individual programme of strength and balance retraining exercises improved physical function and was effective in reducing falls and injuries in women 80 years and older.     

Randomised controlled trial of aminosidine (paromomycin) v sodium stibogluconate for treating visceral leishmaniasis in North Bihar, India

OBJECTIVES: To assess the efficacy and tolerability of aminosidine compared with sodium stibogluconate for treating visceral leishmaniasis. DESIGN: Randomised, unblinded, controlled trial with 180 day follow up. SETTING: Kala-Azar Research Centre, Brahmpura, Muzaffarpur, Bihar, India. SUBJECTS: People of either sex aged 6-50 years with symptoms and signs suggestive of visceral leishmaniasis (fever, loss of appetite, enlarged spleen) with leishmania amastigotes detected in Giemsa stained aspirates of spleen or bone marrow. INTERVENTIONS: Aminosidine at three daily doses (12, 16, and 20 mg/kg) for 21 days and sodium stibogluconate 20 mg/kg/day for 30 days. MAIN OUTCOME MEASURES: Laboratory measures of efficacy: parasite count, haemoglobin concentration, white cell count, platelet count, serum albumin concentration. Clinical measures of efficacy: spleen size, fever, body weight, and liver size. Measures of safety: liver and renal function tests, reports of adverse events. RESULTS: Of the 120 patients enrolled (30 per treatment arm), 119 completed treatment and follow up. Cure at end of follow up was achieved in 23 (77%), 28 (93%), and 29 (97%) patients treated with 12, 16, and 20 mg aminosidine/kg/day respectively, and in 19 (63%) patients given sodium stibogluconate. At 16 and 20 mg/kg/day, aminosidine was significantly more active than sodium stibogluconate in both clinical and laboratory measures of efficacy. No significant clinical or laboratory toxicity occurred in any treatment group. CONCLUSIONS: A 21 day course of aminosidine 16 or 20 mg/kg/day should be considered as first line treatment for visceral leishmaniasis in Bihar.     

A case of bilateral optic neuropathy and recurrent transverse myelopathy associated with perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA)

The purpose of this study was to evaluate skeletal and dental effects of bionator headgear combination appliances on patients in development period with Class II, division 1 malocclusion. The comparison of computerized X-ray cephalometric measurements between the 26 treated children and 26 untreated children was made. The results showed that ANB angle was significantly reduced and horizontal mandibular growth development tended to be normal in the treated group. It was suggested that the bionator headgear combination appliance can restrain the maxillary growth early and promote the forward mandibular growth which contribute the functional jaws correction.     

Elastin-derived peptides and anti-elastic antibodies in children with recurrent or obstructive bronchitis

The aim of the study was to examine the effects of bronchitis on elastin-derived peptides (EP) and antielastin antibodies (AEAb) in serum. Using an ELISA technique, these parameters were assessed in children aged 6 months to 15 years: 36 had recurrent bronchitis (RB), 34 had obstructive bronchitis (OB) and 37 were healthy children (C). A comparison of the levels of the investigated compounds in the acute phase (I) and stage without signs of diseases (II) was studied. The EP data show non-significant changes in the RB and OB groups in comparison with group C. Children with OB had significantly lower levels of AEAb in IgA, IgG and IgM class antibodies, while those with RB in the IgG class in comparison with group C in both examinations. In examination 1, AEAb in IgA and IgM classes were significantly lower in children with OB than with RB.     

Alterations of lymphocyte subsets in patients with recurrent fetal wastage positive for antiphospholipid antibodies treated with Chinese herbal medicine

The delay technique is an established method of enhancing flap survival. This investigation attempts to determine which of two delay techniques results in the best delay effect by measuring their relative abilities to capture adjacent vascular territories in a rat model. A dorsal flap based on the iliac branch of the iliolumbar artery with a captured random zone corresponding to the axial territory of the lateral thoracic artery was used in the evaluation. Sprague-Dawley rats (350-400 g) were randomly assigned into three groups. Group I was the control group. In group II, the circumferential borders of the animal's dorsum were incised without undermining and the dominant pedicle of the lateral thoracic flap was divided. In group III, the medial and lateral borders of the flap were incised and undermined as a bipedicled flap, violating the musculocutaneous perforators. The dominant pedicle of the lateral thoracic artery was also divided. Group III had the greatest survival with only 9% of flap area necrosis compared to 28% and 21% for groups I and II, respectively. These differences were statistically significant. The results suggest that musculocutaneous perforators provide a substantial vascular source to the tissue at risk and should be considered in selecting a delay technique.     

Different anticoagulant and immunological properties of anti-prothrombin antibodies in patients with antiphospholipid antibodies

Lupus anticoagulant (LA) antibodies are acquired inhibitors of coagulation belonging-together with anticardiolipid (aCL) antibodies-to the family of antiphospholipid antibodies. Since LA antibodies affect coagulation reactions via recognition of the complex of lipid-bound prothrombin, they may be better named anti-prothrombin antibodies. We studied their immunological properties in the plasma of 59 patients with antiphospholipid antibodies by means of specific ELISA systems that allowed the characterization of the interaction of these antibodies with human prothrombin and anionic phospholipids. The mode of presentation of prothrombin was found to greatly influence the reactivity of anti-prothrombin antibodies. In fact, when plain polystyrene plates were used to immobilize prothrombin, virtually no binding was observed. Conversely, when prothrombin was coated on high-activated PVC ELISA plates, 34 samples (58%) contained antibodies that recognize human prothrombin in solid phase. In particular, IgG antibodies were found in 21 plasmas and IgM in 22; both IgG and IgM isotypes were present in 9 of these cases. A higher prevalence was observed in the ELISA for the detection of the antibodies directed at the calcium-mediated complex of phosphatidylserine (PS)-bound prothrombin: 53 samples (90%), preadsorbed with cardiolipin liposomes to remove aCL antibodies, showed the presence of IgG and/or IgM anti-prothrombin antibodies. When the results were analyzed according to the immunoglobulin isotypes, 44 (75%) and 39 (66%) samples were found to contain IgG and IgM anti-prothrombin antibodies, respectively. Both IgG and IgM were present in the plasma of 30 patients. Only half of these samples reacted also with PVC-bound prothrombin. Apparently, the higher rate of positivity of the ELISA for the detection of antibodies to the complex of PS-bound prothrombin was not due to differences in the amount of antigen available in the 2 systems, as judged by binding experiments performed with a rabbit polyclonal anti-human prothrombin antiserum. Finally, the anticoagulant properties of 14 total IgG preparations (12 of them contained anti-prothrombin antibodies positive in both ELISA systems, whereas the other 2 cases reacted either with PVC-bound prothrombin only or with PS-bound prothrombin only) were evaluated by diluted Russell's Viper Venom Time and by diluted activated Partial Thromboplastin Time. To rule out the beta 2-glycoprotein I (beta 2-GPI)-dependent anticoagulant effect of the aCL antibodies contained in the preparations, the coagulation tests were performed in beta 2-GPI deficient plasma. Six preparations failed to show anticoagulant activity in both assay systems, suggesting that 2 types of IgG anti-prothrombin antibodies exist, that differ with respect to their anticoagulant properties. These findings suggest that anti-prothrombin antibodies resemble aCL antibodies with respect to the behaviour in "in vitro" coagulation reactions and underline the wide heterogeneity of antiphospholipid antibodies.     

A randomised controlled trial of a low-molecular-weight heparin (Enoxaparin) to prevent deep-vein thrombosis in patients undergoing vascular surgery

The incidence of postoperative deep vein thrombosis (PDVT) after aortic surgery and lower limb revascularisation has not been assessed by a large prospective study. In a prospective randomised trial the effect of a low-molecular-weight heparin fragment, Enoxaparin (ENX) 4200 anti factor Xa IU once daily was compared to that of unfractionated heparin (UFH) 7500 IU twice daily. Two hundred and thirty-three consecutive patients were classified into three groups, aortic or aortoiliac and aneurysmectomy (n = 75), aorto-femoral bypass for atherosclerotic disease (n = 71), and femoropopliteal or femorodistal bypass (n = 87). Patients were analysed for development of deep vein thrombosis by Duplex scanning and, if positive, by venography between the seventh and tenth postoperative day. PDVT was present in 10 patients in the ENX group and in four patients in the UFH group (8.2 and 3.6% respectively, NS). The incidence of PDVT was 8% after aortic or aortoiliac aneurysmectomy, 7% after aortofemoral revascularisation, and 3.4% after femoropopliteal or femorodistal bypass. The overall incidence of PDVT after aortic surgery was 7.5% (95% CI 5.4-9.7). There was no pulmonary embolism. Intra-operative blood loss and postoperative bleeding events did not differ significantly between the ENX and UFH groups. After 1 month follow-up, no clinical event or death could be related to PDVT or pulmonary embolism. In conclusion, in vascular surgery ENX is as safe and effective in the prevention of PDVT as is UFH.     

A four-year randomized controlled trial of hormone replacement and bisphosphonate, alone or in combination, in women with postmenopausal osteoporosis

The aim of this study was to investigate the extent of natural intrinsic fluorescence in carious human dentine and any correspondence of such autofluorescence (AF) to the mineral distribution within the lesion. Two investigative techniques were used, both employing the same sample set and fields in diamond-polished block surfaces of polymethylmethacrylate-embedded carious teeth. AF at emission wavelengths >515 nm, excited by 488-nm laser light, was assessed using a confocal laser scanning optical microscope (CLSM), the recordings made under standard operating conditions. The relative mineral content was assessed using digital backscattered scanning electron microscopy (20 kV BSE-SEM). The AF intensity correlated with the level of demineralisation as seen by BSE, but the depth of the lesion as seen by CLSM was significantly greater implying that the AF is not directly related to the mineral component.     

Randomised controlled trial of novel, simple, and well supervised weight reducing diets in outpatients

OBJECTIVES: To investigate the contribution of novelty and simplicity to compliance with a low energy diet among obese outpatients. DESIGN: Three arm randomised trial for 16 weeks. SETTING: NHS hospital obesity clinic. SUBJECTS: 45 patients aged over 17 years with a body mass index >27 who were not diabetic, pregnant, or lactating. INTERVENTIONS: Conventional 3.4 MJ diet (control), isoenergetic novel diet of milk only, or milk plus one designated food daily. Follow up visit every 4 weeks. MAIN OUTCOME MEASURE: Weight loss. RESULTS: Mean weight loss (kg) after 16 weeks on control, milk only, and milk plus diets was 1.7 (95% confidence interval 0.3 to 3.7), 9.4 (5.9 to 12.9), and 7.0 (2.7 to 11.3) respectively. Weight loss on the novel diets was significantly greater than on the control diet. CONCLUSIONS: Dietary treatment can achieve as much weight loss in obese outpatients over 16 weeks as has been reported for the most successful drug treatment, but compliance with the prescribed diet is poor unless the diet is novel and simple.