Subclinical mastitis as a risk factor for mother-infant HIV transmission.

Subclinical mastitis, as diagnosed by an elevated sodium/potassium ratio in milk accompanied by an increased milk concentration of the inflammatory cytokine, interleukin-8 (IL8), was found to be common among breast feeding women in Bangladesh and Tanzania. Subclinical mastitis results in leakage of plasma constituents into milk, active recruitment of leukocytes into milk, and possible infant gut damage from inflammatory cytokines. Therefore, we wished to investigate whether subclinical mastitis was related to known risk factors for postnatal mother-to-child HIV transmission, that is, high milk viral load or increased infant gut permeability. HIV-infected South African women were recruited at the antenatal clinic of McCord's Hospital, Durban. Risks and benefits of different feeding strategies were explained to them and, if they chose to breast feed, they were encouraged to do so exclusively. Women and infants returned to the clinic at 1, 6 and 14 weeks postpartum for an interview about infant health and current feeding pattern, a lactulose/mannitol test of infant gut permeability, and milk sample collection from each breast separately for analysis of Na/K ratio, IL8 concentration and viral load in the cell-free aqueous phase. Only preliminary cross-sectional analyses from an incomplete database are available at this point. Moderately (0.6-1.0) or greatly (>1.0) raised Na/K ratio was common and was often unilateral, although as a group right and left breasts did not differ. Considering both breasts together, normal, moderately raised or greatly raised Na/K was found, respectively, in 51%, 28%, 21% of milk samples at 1 week (n=190); 69%, 20%, 11% at 6 weeks (n=167); and 72%, 16%, 12% at 14 weeks (n=122). IL8 concentration significantly correlated with both Na/K and viral load at all times. Na/K correlated with viral load at 1 and 14, but not 6 weeks. At 1 and 14 weeks, geometric mean viral loads in samples with Na/K > 1.0 were approximately 4 times those in samples with Na/K < 0.6. At 1 week but not later times, exclusive breast feeding was associated with lower milk viral load than was mixed feeding. Gut permeability was unrelated to milk Na/K ratio or IL8 concentration and was not significantly increased by inclusion of other foods than breast milk in the infant's diet. The results suggest that subclinical mastitis among HIV-infected women may increase the risk of vertical transmission through breast feeding by increasing milk viral load. The importance of various causes of subclinical mastitis, which likely differ at 1 week from at later times and may include local infection or sterile inflammation, systemic infection, micronutrient deficiencies, or poor lactation practices, needs to be further clarified so that appropriate interventions can be implemented.

The growth of segmental nerves from the brachial myotomes into the proximal muscles of the chick forelimb during development.

A study has been made of the growth of segmental nerves 13 to 16 (SN13 to SN16) into the chick limb bud, from the time when they have just reached the ends to the brachial myotomes (stage 21: Hamburger and Hamilton, '51), until they enter the newly formed ventral (stage 24) and dorsal (stage 25) pre-muscle cell masses in the limb bud. At stage 22 axon bundles of SN13 to SN16 have grown off the ends of their respective myotomes, and converge towards the most densely packed mesenchyme in the limb bud at segmental level 15. As a consequence, the first axon bundles of SN14 and SN16 have almost joined those of SN15, whereas the further removed SN13 axon bundles have not yet reached the level of SN15. By stage 23 the first axon bundles from SN14 to SN16 have joined at segmental level 15 to form a nerve which grows toward the ventral pre-muscle cell mass. At stage 24 axon bundles from SN13 have joined those from SN14 to SN16 to form the brachialis longus inferior nerve, which enters the densest region of the ventral pre-muscle. Other axons from SN13 to SN15 grow along the pathways provided by the early arriving axon bundles towards the ventral pre-muscle, but diverge from those at segmental level 14 to grow to the dorsal pre-muscle. By stage 25 axon bundles from SN13 to SN15 have joined to form the brachialis longus superior nerve which enters the densest region of the dorsal pre-muscle. At stage 26 a plexus has formed due to this pattern of growth of the segmental nerves between stages 22 and 25. It is suggested that pre-muscle cells synthesize a nerve growth factor which directs the growth of axons into the limb bud.