A randomised controlled trial of mifepristone in combination with misoprostol administered sublingually or vaginally for medical abortion up to 13 weeks of gestation

OBJECTIVE: To assess women's acceptability, the efficacy and side effects of sublingual versus vaginal administration of misoprostol in combination with mifepristone for medical abortion up to 13 weeks of gestation. DESIGN: Randomised controlled trial. SETTING: Aberdeen Royal Infirmary. POPULATION: Women undergoing medical abortion under the terms of the 1967 Abortion Act. METHODS: Mifepristone (200 mg) was given orally followed 36-48 hours later by misoprostol administration (sublingual: 600 microg; vaginal: 800 microg). A second dose of misoprostol 400 microg was given 3 hours later (sublingually or vaginally). Women between 9 and 13 weeks of gestation received a further (third) dose of misoprostol 400 microg (sublingually or vaginally), 3 hours later if abortion had not occurred. MAIN OUTCOME MEASURES: Women's acceptability, efficacy of the regimen and side effects experienced. RESULTS: A total of 340 women were recruited (171 sublingual and 169 vaginal). A total of 70% of women in the sublingual group expressed satisfaction with the route of misoprostol administration; 18% answered 'Don't know' while 12% were dissatisfied, compared with 68%, 28% and 4%, respectively, in the vaginal group (P= 0.02). There was no significant difference in the need for surgical evacuation for women in the sublingual (3/158, 1.9%) and vaginal groups (4/156, 2.6%) (P= 0.70). Women receiving misoprostol sublingually were more likely to experience diarrhoea (P < 0.01), shivering (P < 0.01) and unpleasant mouth taste (P < 0.01). CONCLUSIONS: Sublingual administration of misoprostol is an effective alternative to vaginal administration for medical abortion up to 13 weeks of gestation. The prevalence of prostaglandin-related side effects, however, was higher with this route of administration.     

Metabolic syndrome and endothelin-1 mediated vasoconstrictor tone in overweight/obese adults

Objective

To determine whether endothelin (ET)-1 vasoconstrictor tone is greater in overweight and obese adults with the metabolic syndrome (MetS).

Materials/Methods

Forty overweight/obese middle-aged and older adults (age: 43–71 years; BMI: 25.1–36.9 kg/m²) were studied: 20 without MetS (13 M/7 F) and 20 with MetS (13 M/7 F). MetS was established according to NCEP ATP III guidelines. Forearm blood flow (FBF; plethysmography) responses to intra-arterial infusion of selective ET_A receptor blockade (BQ-123; 100 nmol/min; for 60 min) and non-selective ET_A/B receptor blockade (BQ-123 + BQ-788 [50 nmol/min for 60 min]) were determined.

Results

In response to the selective ET_A antagonism, there was a significant increase in forearm blood flow from baseline in both groups. However, the increase in forearm blood flow was significantly higher (P = 0.03; ~ 45%) in the overweight/obese group with MetS than the group without MetS. In contrast, there were no significant group differences in FBF responses to non-selective ET_A/B receptor blockade. Peak vasodilator responses to nonselective ET_A/B blockade were ~ 50% higher than baseline blood flow in the overweight/obese groups without and with MetS.

Conclusion

MetS is associated with higher ET-1 vasoconstrictor tone in overweight/obese adults. The enhanced ET-1 vasoconstrictor activity with MetS is mediated by the ET_A receptor subtype.     

Placental abruption and placental hemorrhage: correlation of sonographic findings with fetal outcome

Sixty-nine cases of placental abruption and placental hemorrhage detected with ultrasonography (US) were reviewed retrospectively to determine whether US findings correlate with fetal outcome. Four patients were lost to follow-up, and in the remaining 65 patients fetal outcome included demise in 12 cases (18%), termination of pregnancy in six (9%), premature delivery of a living infant in 15 (23%), term delivery of an infant who was small for gestational age in four (6%), and normal term delivery in 28 (43%). Fetal mortality correlated best with the estimated percentage of placental detachment, but was also significantly (P less than .01) associated with the location (retroplacental) and size (greater than 60 ml) of hemorrhage. Premature labor was associated (P less than .001) only with gestational age at the time of clinical presentation. No sonographic finding was identified as a risk factor for small-for-gestational-age infants. Sonographic findings of placental abruption correlate with fetal outcome, and this information may be useful for guiding obstetric management.     

Idiotypic vaccination against human B-cell lymphoma. Rescue of variable region gene sequences from biopsy material for assembly as single-chain Fv personal vaccines

Idiotypic determinants on neoplastic B cells could provide tumor antigens for vaccination of patients with B-cell tumors. Because this approach requires an individual vaccine for each patient, simple methods for obtaining idiotypic antigen are desirable. Using polymerase chain reaction (PCR) with family-based V-gene and J-region primers, the variable region genes of heavy and light chains (VH and VL) of Ig have been obtained from biopsy material from 13 patients with B-cell tumors. In each case, analysis of random clones derived from the PCR product showed repeated, clonally-related sequences, whereas normal lymphoid tissue generated no repeated sequences. In 3/3 cases, the repeated sequences were found to be the same as those in a tumor-derived hybridoma. Mutational patterns in the V-genes differed among the tumors, with follicular lymphoma tending to be more highly mutated. The individual VH and VL sequences have been assembled with a flexible linker sequence to encode single-chain Fv (scFv). The scFv sequences can be cloned into bacterial expression vectors to produce protein, or into vectors suitable for direct vaccination using naked DNA. In a model system, expressed scFv protein retained all idiotypic determinants defined by a panel of five anti-idiotypic monoclonal antibodies (MoAbs). Similarly, expressed scFv proteins from two patients were shown to react with anti-idiotypic antibodies. This approach allows production of potential vaccines from surgical biopsies within 2 to 3 weeks.     

Comparison of measured sleeping metabolic rate and predicted basal metabolic rate in the first year of life

In infants, sleeping metabolic rate (SMR) is used as a proxy for basal metabolic rate (BMR). BMR can be predicted from anthropometry using published equations. Our study was intended to evaluate the ability of these equations to predict measured SMR in infants aged 6 weeks to 12 months. SMR was measured in a mixed longitudinal study using the Douglas bag technique ( n = 105). Measured SMR values were compared with BMR predicted from weight (BMR-1) or weight and length (BMR-2). These equations were not successful in predicting SMR in this age group. Percentage error of predicted BMR was related to infant weight (BMR-1: r = 0.26; p < 0.005; BMR-2: r = 0.18; p < 0.06). Alternative logarithmic equations were derived from this study (R = 0.84-0.87; SEE = 0.159-0.168). We conclude that the new equations, relating to contemporary infants, are more suitable but actual measurements remain preferred.     

Comparison of Fyb status as determined serologically and genetically

Comparison of the serologically determined phenotype and the genotype of samples as defined by PCR-RFLP indicated a significant percentage of discrepancies on analysis of serologically defined Fy(+b−) samples. An investigation of these discrepancies has shown that the serologically determined phenotype of the samples varies with respect to the reagent used but that the PCR-RFLP assay gives reliable results for all the samples investigated. The samples which yielded the discrepant results were further investigated and the results indicated weakened expression of the Fy^b antigen. This may arise by a method similar to the expression of Fy^x although we found the incidence of these samples to be much higher than that reported for Fy^x. These results may have important implications for the routine testing of blood donations, particularly in situations where the unit is to be transfused to a patient who has previously formed an anti-Fy^b.     

Anti-melanoma cytotoxic T lymphocytes (CTL) recognize numerous antigenic peptides having 'self' sequences: autoimmune nature of the anti-melanoma CTL response

A line of tumor-infiltrating lymphocytes (660TIL) specifically lysed the autologous HLA-A2+ melanoma (660MEL) and also most A2+ melanoma cell lines. We immunoprecipitated A2 from a large number (>10(12)) of 660MEL cells, extracted naturally processed peptides, fractionated them by HPLC, screened the fractions for recognition by 660TIL, and found a single predominant and a minor peak of activity. Although too little was recovered of the major 660MEL peptide to establish its sequence, HPLC fingerprinting showed that it did not correspond to any of the known A2-associated melanoma peptides recognized by T cells, including peptides from tyrosinase, MART-1/Melan-A, gp100 and MAGE-3. The major 660MEL antigenic peptide appears to be derived from MART-1/Melan-A but is neither AAGIGILTV nor ILTVILGVL nor any other MART-1/Melan-A peptide containing the A2 consensus motif. The multiplicity of melanoma peptides recognized by CD8+ T cells, most of which are non-mutated (including most likely the present 660MEL peptide), suggests the existence of unknown mechanisms, perhaps similar to those operating in autoimmune disorders, whereby T cells that recognize normal 'self' sequences become activated.