Early diet in preterm babies and developmental status at 18 months.

424 preterm infants were randomly assigned a standard "term" formula or a nutrient-enriched "preterm" formula as sole diets (trial A) or as supplements to mother's own expressed milk (trial B) for a median of 4 weeks postnatally. 18 months post term, blind evaluation of 377 survivors showed that those previously fed preterm rather than term formula had major developmental advantages, more so in motor than mental function; the advantages, in both mental and motor scores, were especially striking in small-for-gestational-age infants and in males. For motor development index in trial A, this advantage was 15 points; in infants born small for gestation, it was 23 points (nearly 1.5 SD). Moderate developmental impairment (developmental index less than 85), notably motor impairment, was considerably more common in the group fed term formula. Infants fed preterm formula also had a small benefit in social maturity quotient. Thus, a short period of early dietary manipulation in preterm infants had major consequences for later development, which suggests that the first weeks may be critical for nutrition.

Mast-cell-deficient W/Wv mice exhibit a decreased rate of tumor angiogenesis.

The role of host mast cells in tumor-associated angiogenesis was investigated by comparing the angiogenic response of genetically mast-cell-deficient W/Wv mice and mast-cell-sufficient +/+ littermate mice to s.c. growing B16-BL6 tumors. The angiogenic response was found to be slower and initially less intense in W/Wv mice than in +/+ mice. Fewer W/Wv mice than +/+ mice developed spontaneous lung metastases and W/Wv mice exhibited fewer lung metastases per mouse. Bone-marrow repair of the mast-cell deficiency restored the angiogenic response of W/Wv mice and also restored the incidence of hematogenous metastases to approach that of +/+ mice. Differences in lymphatic metastasis were not detected between W/Wv and +/+ mice. These results demonstrate a role for mast cells in vivo during tumor angiogenesis, and suggest a role also for host mast cells in hematogenous metastasis.

Early sodium intake and later blood pressure in preterm infants.

The relation between early salt intake and later hypertension is debated. As part of a larger feeding study, 347 preterm infants were randomly assigned to receive early diets differing grossly in sodium content. Feeding a high sodium preterm formula in the neonatal period did not influence arterial blood pressure at 18 months (corrected) age.

Maternal fatness and viability of preterm infants.

To investigate the effect of maternal fatness on the mortality of infants born preterm up to the corrected age of 18 months 795 mother-infant pairs were studied. Maternal fatness was defined by Quetelet's index (weight/(height] and all infants weighed less than 1850 g at birth. In 771 mother-infant pairs maternal age, complications of pregnancy, mode of delivery, parity, social class, and the baby's sex and gestation were analysed by a logistic regression model for associations with infant mortality (but deaths from severe congenital abnormalities and those occurring during the first 48 hours after birth were excluded). In a subgroup of 284 mother-infant pairs all infant deaths except those from severe congenital abnormalities were analysed in association with the infant's birth weight and gestation and the mother's height and weight; this second analysis included another 24 infants who had died within 48 hours after birth. In the first analysis mortality overall was 7% (55/771), rising from 4% (71/173) in thin mothers (Quetelet's index less than 20) to 15% (6/40) in mothers with grades II and III obesity (Quetelet's index greater than 30). After adjusting for major demographic and antenatal factors, including serious complications of pregnancy, maternal fatness was second in importance only to length of gestation in predicting death of infants born preterm. In the second analysis mortality overall was 15% (44/284), rising from 9% (5/53) in thin mothers to 47% (8/17) in mothers with grades II and III obesity. In both analyses the relative risk of death by 18 months post-term was nearly four times greater in infants born to obese mothers than in those born to thin mothers. In addition, maternal fatness was associated with reduced birth weight, whereas it is associated with macrosomia in term infants. These data differ fundamentally from those reported in full term babies of obese mothers. It is speculated that the altered metabolic milieu in obesity may reduce the ability of the fetus to adapt to extrauterine life if it is born preterm.

Factors associated with maternal choice to provide breast milk for low birthweight infants.

Factors associated with maternal choice to provide milk for premature infants were investigated in 925 mother/infant pairs in five hospitals. A well educated, married, primiparous mother aged 20 or over who delivered a baby boy by caesarean section was nearly 1000 times more likely to choose to express her milk than a mother who was poorly educated, single, multiparous, and aged under 20, delivering a female infant vaginally. Evidence from the five centres suggested that hospital staff have little influence on a mother's choice of feeding method. The major differences between the populations of babies whose mothers do or do not choose to provide milk, raise important issues concerning the interpretation of data from non-randomised clinical trials of feeding premature infants.

Immune response potential of mast cell-deficient W/Wv mice.

Immune responses of mast cell-deficient WBB6F1-W/Wv mice and their mast cell-sufficient littermates (LM: WBB6F1-W/+, Wv/+ and +/+) were compared. After a single intravenous injection of sheep erythrocytes (SE), polyvinylpyrrolidone or bacterial lipopolysaccharide, the antigen-specific IgM plaque-forming cell (PFC) response of W/Wv mice was similar to or greater than the response of LM mice. When both primary and secondary injections of SE or chicken gamma-globulin were given to mice and antigen-specific IgG PFC responses quantified, the response of W/Wv again was similar to or greater than that of LM mice. Serum titers of antigen-specific IgE were higher in W/Wv than in LM mice after injections of ovalbumin in alum or infections of Nippostrongylus brasiliensis. Ovalbumin-sensitized W/Wv and LM mice developed active systemic anaphylaxis after ovalbumin challenge. The ability of W/Wv mice to be sensitized for and elicit contact sensitivity (CS) reactions was studied using picryl chloride or dinitrofluorobenzene as sensitizing and challenge agents and quantifying 24-hour reactions by change in ear thickness. SE or methylated bovine serum albumin was used to sensitize and challenge mice for delayed-type hypersensitivity (DTH) reactions which were quantified at 24 h by change in foot pad or ear thickness. CS and DTH reactions of W/Wv and LM mice were similar. No evidence of immune deficiency of W/Wv mice was found.

X-linked dominant chondrodysplasia punctata: a case report and family studies.

Two major types of chondrodysplasia punctata have been delineated; a severe, recessively inherited, rhizomelic form and the less severe, dominantly inherited Conradi-Hünerman form. Clinico-genetic analysis of this latter form of CP uncovered a sub-group characterised by asymmetric involvement with linear or whorled skin patches of ichthyosiform erythroderma or atrophoderma, circumscribed cicatricial alopecia, asymmetrical cataracts and limb shortness. The mosaic pattern of the manifestations and the limitation of reported cases to females suggested an X-linked dominant gene which undergoes Lyonisation in the female and is lethal in the hemizygous male. We report on a family ascertained through a baby girl who had manifestations typical of the X-linked dominant form of CP and whose mother, 2 of 3 maternal aunts, and maternal grandmother all had less severe manifestations. The absence of male offspring for 3 generations and a history of 3 early miscarriages, along with the clinical variability in the affected females, provide further support for X-linked dominant inheritance of this disorder.

Bone marrow origin of mucosal mast cells.

Infection with the intestinal parasite Nippostrongylus brasiliensis stimulates an accumulation of mucosal mast cells (MMC) in the villi of the small intestine of normal but not athymic or W/Wv anemic mice. W/Wv mice are congenitally deficient in both MMC and skin and connective tissue mast cells (CTMC). Athymic mice have normal or elevated numbers of CTMC but are severely deficient in MMC. CTMC derive from the bone marrow. To determine the origin of MMC, athymic and W/Wv mice were given various hematopoietic or lymphoid tissues from normal littermate or beige mice and the MMC response to N. brasiliensis infection was evaluated. The MMC defect in athymic mice was repaired by grafts of thymus cells, thymus gland, or spleen cells, but not by bone marrow cells or anti-Thy 1-treated bone marrow or spleen cells. The MMC and CTMC defects of W/Wv mice were repaired by grafts of bone marrow, spleen cells, or anti-Thy 1-treated bone marrow or spleen cells. Neither the MMC nor the CTMC defect in W/Wv mice was repaired by grafts of thymus cells or thymus glands. These results indicate the following, MMC, like CTMC, derive from the bone marrow and not from the thymus. MMC require a thymic influence for development. Athymic mice possess bone marrow precursors for both MMC and CTMC but lack a thymus-dependent component necessary for MMC development. W/Wv mice lack both MMC and CTMC mast cell precursors but possess the thymus-dependent component required for MMC development.

Delayed expulsion of adult Trichinella spiralis by mast cell-deficient W/Wv mice.

Mast cell-deficient W/Wv mice and their mast cell-sufficient littermates were given infections of Trichinella spiralis. W/Wv mice were slower than their littermates to expel adult T. spiralis. Repair of the mast cell deficiency of W/Wv mice by bone marrow grafting was accompanied by accelerated expulsion of T. spiralis.

Mucosal mast cell reconstitution and Nippostrongylus brasiliensis rejection by W/Wv mice.

The ability of congenitally mast cell-deficient W/Wv anemic mice and mast cell-reconstituted W/Wv mice to reject the intestinal parasite Nippostrongylus brasiliensis was examined. The W/Wv mice were deficient in connective tissue mast cells and mucosal mast cells and, unlike normal mice, did not accumulate intestinal mucosal mast cells in response to N. brasiliensis infection. They had higher peak egg counts than did normal littermates and were slower than littermates to reject the parasites. Reconstitution with bone marrow or spleen cells repaired both the connective tissue and mucosal mast cell defects in W/Wv mice but did not alter the time of parasite rejection or decrease the high peak egg counts. These results indicate that mucosal mast cells that accumulate in the small intestine in response to parasite infection may not be functionally involved in the rejection mechanism.

Characteristics of mast cells in Chediak-Higashi mice: light and electron microscopic studies of connective tissue and mucosal mast cells.

The beige mouse, a homologue of the Chediak-Higashi syndrome in man, possesses abnormally large granules in many tissue cells. The granules in the mucosal mast cells (MMC) of the small intestine of beige and littermate C57BL/6J mice were examined after infecting the mice with the intestinal parasite, Nippostrongylus brasiliensis. MMC in both beige and littermate mice had irregular granules which contained paracrystalline substructures embedded in an amorphous matrix. Granules were not observed in fusion with the cell membrane. Instead, in late-stage mast cells, the granule membrane broke down, the granule contents were spread throughout the cytoplasm, and the cell organelles disintegrated. Unlike connective tissue mast cells, MMC were poorly demonstrated with formalin fixation and toluidine blue staining.

Rejection of the intestinal parasite Nippostrongylus brasiliensis by mast cell-deficient W/Wv anemic mice.

The ability of W/Wv anemic mice to accumulate mucosal mast cells and to reject the intestinal parasite Nippostrongylus brasiliensis was examined. W/Wv mice did not accumulate mucosal mast cells in response to infections with N. brasiliensis. They eliminated a primary infection more slowly than did their normal littermate controls but were as refractory as controls to second and third infections. W/Wv mice had higher serum titers of worm-specific immunoglobulin E than did controls. These results indicate that mucosal mast cells are not an absolute requirement for N. brasiliensis rejection.

A form of metatropic dwarfism in two brothers.

Two brothers are described with identical features of short-limbed dwarfism, normal face, hands and feet, respiratory difficulties and mild scoliosis. It proved impossible to offer a definitive diagnosis, though radiological features as a whole bore similarities to those of metatropic dwarfism, with the most notable feature the narrowing of the ossified components of the vertebral bodies.