A patient with Graves' disease, thrombocytopenia and chronic hepatitis B

A 22-year-old Chinese man, a HBsAg carrier, presented with relapse of thyrotoxic Graves' disease complicated by thrombocytopenia and hepatitis. Platelet count and liver enzymes gradually improved following successful treatment of the thyrotoxicosis with radioactive iodine. Possible pathogenetic links and therapeutic implications are discussed.     

Patterns of clinical metastasis in breast cancer: an analysis of 100 patients

Many patients diagnosed with breast cancer will develop metastases and these have diverse presentations. We have reviewed 100 consecutive patients who have died with metastatic breast cancer, to determine the frequency, sites and mode of presentation of recurrent disease. The commonest site of failure was loco-regional (n = 61), this usually presented with a mass, but a minority of patients also complained of pain. Bone metastases developed in 60 patients and produced bone pain, pathological fracture (n = 6) or cord compression (n = 5). Pulmonary metastases producing shortness of breath were diagnosed in 34 patients and were asymptomatic in a further 10. Intra-abdominal metastases were found at some time in 23 patients, most commonly in the liver (n = 20) and the majority complained of epigastric pain (n = 17). Brain metastases occurred in 23 patients and produced a wide range of symptoms including those of a space-occupying lesion (n = 10), cranial nerve palsy (n = 7), diabetes insipidus (n = 3), focal limb weakness (n = 2) and meningitis (n = 1). Three patients had choroid metastases producing reduced visual acuity. Recurrent breast carcinoma can present in a variety of ways, therefore any new symptom or sign should be considered to represent recurrence until proved otherwise.     

Is apoptosis involved in mechanisms to eliminate Onchocerca ochengi during Simulium damnosum s.l. immune response?

Co-injection of the parasite Onchocerca ochengi and the caspase inhibitors z-VAD.fmk and boc-D.fmk into the natural vector Simulium damnosum s.l. led to significantly increased survival of the parasites. Subsequent in situ apoptosis detection assays demonstrated that in the case of boc-D.fmk the enhanced survival was due to a diminished apoptosis level of the microfilariae in vivo. Additional assays using O. ochengi microfilariae which were coinjected with serine protease inhibitors into S. damnosum s.l. revealed that certain serine protease inhibitors can reduce the level of apoptosis.     

Expectancy for social facilitation from drinking: the divergent paths of high-expectancy and low-expectancy adolescents

Using a 3-wave longitudinal design, adolescents were studied over a 2-year period during which many first began to drink. Covariance structure modeling showed that teens' expectancy for social facilitation from alcohol and their drinking experience influenced each other in a reciprocal, positive feedback fashion: the greater the expectancy endorsement, the higher subsequent drinking levels, and the higher the drinking levels, the greater the subsequent expectancy endorsement. This model fit the data quite well; comparison models, in which expectancy (or drinking) had no independent influence on future drinking (or expectancy), showed significantly poorer fit than the present model. Initial nondrinkers' social expectancy predicted individual differences in the rate of drinking increase over the 2 years. Results bolster the hypothesis that expectancy actively influences drinking and point to the importance of expectancy-based intervention efforts.     

Synthesis and in vitro activity of some epimeric 20 alpha-hydroxy, 20-oxime and aziridine pregnene derivatives as inhibitors of human 17 alpha-hydroxylase/C17,20-lyase and 5 alpha-reductase

Some epimeric 20-hydroxy, 20-oxime, 16 alpha, 17 alpha-, 17,20- and 20,21-aziridine derivatives of progesterone were synthesized and evaluated as inhibitors of human 17 alpha-hydroxylase/C17,20-lyase (P450(17) alpha) and 5 alpha-reductase (5 alpha-R). The reduction of 16-dehydropregenolone acetate (3a) was reinvestigated. NaBH4 in the presence of CeCl3 gave better stereo-selectivity for 20 beta-ol [20 alpha/20 beta-OH (4 alpha/4 beta) = 1/2.7] than LTBAH or the Meerwein-Pondroff method reported; reduction with Zn in HOAc formed exclusively 20 alpha-ol (4 alpha b). The 20 alpha- and 20 beta-hydroxy-4,16-pregnadien-3-one (9 alpha) and (9 beta) were synthesized from the alcohols 4 alpha b and 4 beta b. Several 20-oxime pregnadienes and 16 alpha, 17 alpha-, 17,20- and 20,21-aziridinyl-5-pregnene derivatives were also synthesized. LiAlH4 reduction of the 16-en-20-oxime (12b) yielded 20 (R)-(13a) and 20(S)-17 alpha,20-aziridine (13b) and 20(R)-17 beta,20-aziridine (14a). Several compounds inhibited the human P450(17) alpha with greater potency than ketoconzole. The 5 alpha-R enzyme assay showed that while (9 alpha) did not have any activity, (9 beta) and (3b) were potent 5 alpha-reductase (IC50 = 21 and 31 nM) inhibitors with activities similar to finasteride. The 20-oximes (17a) and (17b) were potent dual inhibitors for both 5 alpha-R (IC50 = 63 and 115 nM, compared to 33 nM for finasteride) and P450(17) alpha (IC50 = 43 and 25 nM, compared to 78 nM for ketoconazole).     

Semi-parametric models for mismeasured exposure information in vaccine trials

Exposure to infection information is important for estimating vaccine efficacy, but it is difficult to collect and inherently prone to missingness and mismeasurement. It is, therefore, generally not feasible to collect good exposure information on all participants in a large vaccine trial. We discuss study designs that collect detailed exposure information for only a small subset of trial participants, while collecting crude exposure information on all participants, and treat estimation of vaccine efficacy in the missing data/measurement error framework. We demonstrate with the example of an HIV vaccine trial the improvements in bias and efficiency when we combine the different levels of exposure information to estimate vaccine efficacy for reducing both susceptibility and infectiousness. We compare the performance of recently developed semi-parametric missing data methods of Pepe and Fleming and Carroll and Wand, Robins, Hsieh and Newey, and Reilly and Pepe.