Fetal growth and autoimmune thyroid disease

To determine whether fetal and infant growth could influencesusceptibility to autoimmune disease in adults, the occurrenceof thyroid autoantibodies and autoimmune thyroiditis was studiedin 305 women, aged 60–71, born in Hertfordshire and forwhom details of birth weight, infant growth, and feeding wereroutinely recorded. Thyroglobulin autoantibody was detectedin 37% of the women, thyroid peroxidase autoantibody in 41%,and autoimmune thyroiditis, defined as biochemical or clinicalhypothyroidism in association with thyroid autoantibodies, in5.6%. The proportion of women with thyroglobulin and thyroidperoxidase auto antibodies fell with increasing birth weightbut was not related to weight at 1 year of age or the methodof infant feeding. The prevalence of both autoantibodies rosewith increasing adult body mass index but fell as the waistto hip ratio increased. These results demonstrate the importance of early environmentin determining the susceptibility to autoimmune thyroid disease.The contrasting effects of adult body mass index and waist tohip ratio on antibody prevalence could be explained by theirassociations with different hormonal environments.     

Effect of norethisterone acetate on serum lipid and lipoprotein parameters as well as on blood coagulation in female monkeys (M. fascicularis)

The effects of daily oral administration of a high dose of 10 mg norethisterone acetate (NET-Ac.)/kg/day over 14 weeks on serum lipid and lipoprotein parameters as well as on blood coagulation were investigated in female monkeys (M. fascicularis). Measurements of lipids and lipoprotein cholesterol were performed in weeks —5 and — 1 before treatment and in weeks 4, 8 and 12 after treatment. In addition, various blood coagulation and fibrinolytic parameters were determined in weeks 11–14 after treatment with NET-Ac. Furthermore, the serum levels of norethisterone (NET) were determined in order to monitor the real systemic compound exposure and revealed that C_max and AUC (0–3 h) values reached for norethisterone in this experiment in monkeys were about 25 times higher than those obtained after an oral contraceptive dose of NET-Ac. in women.

The results of lipid and lipoprotein cholesterol determinations showed decreases in serum total lipids, phospholipids, triglycerides and total cholesterol associated with similar decreases in HDL-, LDL- and VLDL-cholesterol fractions after NET-Ac.-treatment in monkeys. These effects were observed from week 4 onwards and maintained their magnitude up to week 12 after treatment. Since both HDL- and LDL-cholesterol fractions decreased, the HDL/LDL-ratio remained almost unchanged. Thus, the results obtained in this study after high-dose treatment with NET-Ac. in monkeys did not indicate any changes of lipid and lipoprotein parameters which in humans are supposed to be associated with an increased risk of cardiovascular lesions, namely a decrease in HDL- and increase in LDL-cholesterol fractions.

The results of blood coagulation and fibrinolytic parameters showed increased antithrombin-III and plasminogen levels besides minor changes in other parameters, thus indicating that NET-Ac. -treatment does not contribute to an increased risk of cardiovascular thrombotic events in the cynomolgus monkey.     

Monocyte chemotactic protein expression during schistosome egg granuloma formation. Sequence of production, localization, contribution, and regulation.

The present study explored the role of murine monocyte chemotactic protein (MCP) in the T cell-mediated hypersensitive granulomatous response to Schistosoma mansoni eggs. The study examined the time course of local production, contribution to cellular infiltration, and the role of T cells in endogenous regulation. Synchronized pulmonary granulomas were induced under conditions of primary and secondary states of immunity. Primer-directed polymerase chain reaction analysis showed increased MCP mRNA expression in granulomatous lungs, mainly in the secondary response. Levels of MCP were measured by enzyme-linked immunosorbent assay in cultures of intact granulomas. Spontaneous MCP production was modest in primary granuloma cultures, reaching a maximum of 5.7 +/- 0.9 ng/ml by 16 days. In contrast, the secondary response showed augmented and accelerated production, achieving 13 +/- 2.0 ng/ml by 2 days. Immunohistochemical staining revealed the strongest MCP expression within microvascular adventitial cells or pericytes as well as in scattered mononuclear cells associated with granulomas. Staining was not detected in normal lungs. Passive immunization with anti-MCP-1 antibodies caused a 40% reduction in the secondary granuloma area but did not significantly affect the primary response. With adoptive cell transfer and T cell subset depletion, it was shown that Thy-1+ and CD5+ cells augmented, whereas CD8+ cells appeared to impair, MCP production. This provides direct evidence that MCP is involved in secondary Th2-mediated response to schistosome eggs and is subject to regulation by T cells.     

Long-term surgical results for congenital aural atresia

Thirty-nine primary surgical cases for correction of congenital aural atresia were reviewed for complications and long-term hearing results. Hearing averages of 25 dB for mild atresia, 40 dB for moderate atresia, and 46 dB for severe atresia were obtained. Serviceable hearing was achieved in 64% of the cases. The two most frequent complications were stenosis and recurrent infections of the cavity and canal skin, with an incidence of 33% and 31%, respectively. Use of split-thickness instead of full-thickness skin graft was associated with fewer complications. The goal of this review is also to share the experience of the senior author in the management of this complex problem.     

Mycobacteriosis due to Mycobacterium genavense in six pet birds.

Six cases of mycobacteriosis due to Mycobacterium genavense in three budgerigars (Melopsittacus undulatus), one orange-winged amazon (Amazona amazonica), one flycatcher (Cyanoptila cyanomelana), and one zebra finch (Taeniopygia guttata) are discussed. Gross lesions associated with the infection included a high degree of muscular wasting (five cases), hepatomegaly (four cases), and thickening of the wall of the small intestine (four cases). Granulomas were found in the lung (one case) and the subcutis (one case). Acid-fast bacilli were detected in the liver of all six birds. Only the use of acidic BACTEC mediums consistently led to growth, whereas the egg-based medium failed. These findings point to a possible role of the environment as a reservoir for M. genavense.     

Effects of Sclerocarya birroea Hochst. extract on some metabolic activities in the rat

The decoction of Sclerocarya birroea Hochst. shows hypoglycaemic effects, an increase in plasma IRI in normal rats and an incremented oral-glucose tolerance. The decoction is also active against diet-induced hypercholesterolaemia.     

Development of an auxotrophic oral live Shigella flexneri vaccine

An oral live attenuated Shigella flexneri vaccine candidate strain was constructed by making it auxotrophic and dependent on aromatic metabolites not available in mammalian tissues. An aroD gene of Escherichia coli K12 strain NK 5131, inactivated by insertion in it of the Tn 10 transposon, was transduced using phage P1 into a virulent S. flexneri serotype Y strain (Sfl 1) isolated from a patient with bacillary dysentery. One of the transductant strains Sfl 114 was found to invade HeLa cells in vitro, to cause plaque formation in HeLa monolayers (i.e. maintain intracellular multiplication in vitro), but to be unable to cause keratoconjunctivitis in guinea-pig eyes. When the strain was fed to Macacca fascicularis monkeys it was well tolerated, excreted for 1-4 days, and found to elicit a local intestinal sIgA and serum IgA, IgM and IgG responses. Monkeys challenged with 100 ID50 dose (1 X 10(11) bacteria) of the virulent parent Sfl 1 strain were completely protected from development of diarrhoea. Coloscopy of the monkeys and the sampling of intestinal biopsies showed that the vaccine protected against the surface epithelial erosions and ulcerations seen in unimmunized monkeys. Killing of invading virulent shigellae apparently took place intracellularly in the mucosa suggesting that cellular immune mechanisms played a role in the elicited host defence. The constructed S. flexneri Sfl 114 strain has the properties of a promising shigella vaccine and will next be the subject of studies with human volunteers.