Effect of diet on infant subcutaneous tissue triglyceride fatty acids

Having demonstrated a deficiency in infant cerebral cortex docosahexaenoic acid of formula fed compared with breast milk fed infants, we sought to identify why the extensive subcutaneous tissue triglyceride fatty acid reserves in term new-born infants appeared to be ineffectual in its prevention. In addition to 24 term and six preterm infants who died from 'cot death', tissue was analysed from four perinatal surgical patients and in the former the results were correlated with dietary milk intake. The higher amounts (about 15% by weight) of unsaturated linoleic acid supplied in the formula milks were quantitatively incorporated into the subcutaneous tissue largely at the expense of the saturated palmitic acid possibly compromising adipocyte fluidity. The six preterm infants were in two formula fed groups and there was only one significant difference, namely a higher subcutaneous tissue concentration of alpha-linolenic acid in one of the preterm groups, distinguishing them from their term counterparts. This may imply that the enzymes involved in absorption and digestion of fatty acids are mature in the preterm infant. From birth the mean weight percentage of docosahexaenoic acid (0.4%) fell rapidly to undetectable levels (< 0.05%) in the formula fed group after about two months. It is therefore concluded that if breast feeding is not possible then a minimum daily requirement of 30 mg docosahexaenoic acid (approximately 0.2 g/100 g fatty acids) should be supplied in formulas designed for term infants to prevent the cerebral cortical deficiency of docosahexaenoic acid.     

Neonatal auditory brainstem response failure of very low birth weight infants: 8-year outcome.

Fifty-six very low birth weight infants (less than 1.5 kg) were followed until 8 y of age to see if predischarge auditory brainstem response (ABR) results were predictive of neurobehavioral development. The results suggest that early ABR may predict subsequent performance on measures of intelligence quotient, language, and reading. Unilateral ABR abnormalities did not appear predictive, but bilateral abnormalities did. Analysis of a variety of neonatal risk factors in conjunction with early ABR and hearing loss with respect to educational outcome was also undertaken.     

The effect of very low birth weight and social risk on neurocognitive abilities at school age.

We tested the hypothesis that very low birth weight (VLBW < 1.5 kg) children would have significantly poorer neurocognitive abilities at school age than would normal birth weight full-term age mates, that differences would persist after control for neurologic impairment and social risk, and that VLBW would interact with social risk. Two hundred forty-nine VLBW children and a randomly selected sample of 363 normal birth weight age mates born 1977 through 1979 were tested at 8 years. A neurologic examination and tests of intelligence, language, speech, reading, mathematics, spelling, visual and fine motor abilities, and behavior were performed. Twenty-four (10%) VLBW had a major neurologic abnormality compared with none of the controls. VLBW had significantly poorer scores on all tests, with the exception of speech and the total behavior score. These differences persisted among VLBW children without major neurologic abnormality, with the exception of social competence, reading, and spelling. Even normal IQ, neurologically normal VLBW had significantly poorer scores than did controls in expressive language, memory, visuomotor, and fine motor function, and measures of hyperactivity. When social risk was controlled in multiple regression analyses, VLBW still had an adverse effect on all outcome measures with the exception of speech. Social risk was, however, the major determinant of outcome. We found an interaction between VLBW and social risk only in verbal IQ and in the opposite direction than hypothesized.     

C1-Esterase inhibitor: an anti-inflammatory agent and its potential use in the treatment of diseases other than hereditary angioedema

C1-esterase inhibitor (C1-Inh) therapy was introduced in clinical medicine about 25 years ago as a replacement therapy for patients with hereditary angioedema caused by a deficiency of C1-Inh. There is now accumulating evidence, obtained from studies in animals and observations in patients, that administration of C1-Inh may have a beneficial effect as well in other clinical conditions such as sepsis, cytokine-induced vascular leak syndrome, acute myocardial infarction, or other diseases. Activation of the complement system, the contact activation system, and the coagulation system has been observed in these diseases. A typical feature of the contact and complement system is that on activation they give rise to vasoactive peptides such as bradykinin or the anaphylatoxins, which in part explains the proinflammatory effects of either system. C1-Inh, belonging to the superfamily of serine proteinase inhibitors (serpins), is a major inhibitor of the classical complement pathway, the contact activation system, and the intrinsic pathway of coagulation, respectively. It is, therefore, endowed with anti-inflammatory properties. However, inactivation of C1-Inh occurs locally in inflamed tissues by proteolytic enzymes (e.g., elastase) released from activated neutrophils or bacteria thereby leading to increased local activation of the various host defense systems. Here we will give an overview on the biochemistry and biology of C1-Inh. We will discuss studies addressing therapeutic administration of C1-Inh in experimental and clinical conditions. Finally, we will provide an explanation for the therapeutic benefit of C1-Inh in so many different diseases.     

Brainstem evoked response audiometry in the premature infant population

Auditory brainstem response (ABR) audiometry was performed on 76 non-selected premature infants from 32 to 40 weeks conceptional age. Follow-up ABR was completed on 45 infants at 4 months of age. The results were compared to data from selected, relatively low risk infants of comparable age. No significant differences were seen between the two groups, which indicates that normative data from non-selected premature infants can be obtained to identify ABR abnormality.     

Very low birth weight infants: effects of brain growth during infancy on intelligence quotient at 3 years of age

To evaluate the role of postnatal growth on IQ at 3 years of age, 139 appropriate for gestational age, very low birth weight infants (less than 1.5 kg) born in 1977 and 1978 were studied at 40 weeks (term), and at 8, 20, and 33 months (corrected) of age. Weight, height, and head circumference were measured at each age, neurologic status was measured at 20 months, and Stanford Binet IQ at 33 months. Multiple regression analysis revealed that head circumference at 8 months of age is the best growth predictor of IQ at 3 years of age. Path analysis was performed to measure the effects of biologic and social factors measured earlier in life on IQ at 3 years. These factors explained 43% of the variance in IQ at 3 years of age. Head circumference at 8 months had a direct effect on IQ at 3 years, controlling for all other variables in the model. Neonatal risk had an indirect effect via head circumference. Neurologic impairment had direct and indirect (via head circumference) effects; race and socioeconomic status had direct effects on IQ but no effects on growth at 8 months of age. Thus, brain growth at 8 months significantly influenced 3 year IQ at 3 years of age among very low birth weight infants, even when medical and sociodemographic variables were controlled.     

Localization and identification of granzymes A and B-expressing cells in normal human lymphoid tissue and peripheral blood.

Cytoplasmic granules from activated natural killer (NK) and cytotoxic T lymphocytes (CTL) contain a pore-forming protein, perforin, and several homologous serine proteinases called granzymes. Expression of these proteins correlates with the cytolytic potential of cytotoxic lymphocytes. Using a panel of MoAbs specific for human granzyme A and B, respectively, expression of these proteinases in non-pathological lymphoid tissue and peripheral blood lymphocyte (PBL) subpopulations was investigated. Using immunohistochemistry and double stainings, the phenotype of granzyme-expressing cells in lymphoid tissue was investigated. Granzyme-positive cells were detected in all lymphoid tissues tested. No large differences in the number and distribution between granzyme A- and granzyme B-positive cells were observed. The highest number of positive cells was located in the red pulp of the spleen. Significant numbers were detected in tonsil, lymph nodes, liver and thymus. Low numbers were present in the lamina propria of non-inflamed stomach, small intestine and colon. Phenotypic analysis and cell sorting showed that most of the granzyme-positive cells in lymphoid tissue and PBL consisted of CD3-CD16+CD56+ lymphocytes. Hardly any granzyme-positive CD3+CD8+ CTL were present in peripheral blood. The synthesis of granzyme A as well as B by both CD3+CD16+CD56+ and CD3+CD8+ cells in peripheral blood was increased upon IL-2 stimulation. These results indicate that in normal lymphoid tissue the predominant cytolytic cell population is formed by the NK cells, and activated CTL are rare.     

Neutrophil activation in ivermectin-treated onchocerciasis patients.

Ivermectin is a safe and effective drug for onchocerciasis treatment. In certain individuals, however, therapy is accompanied by adverse reactions. The mechanisms underlying these reactions are not yet known. The aim of the present study was to investigate whether neutrophils are involved in the development of these adverse reactions. Elastase and lactoferrin, two markers for the release of neutrophil azurophilic and specific granule contents respectively, were measured by radioimmunoassays in plasma of onchocerciasis patients with varying degrees of side effects, as well as in control subjects before and 1 and 2 days after ivermectin treatment. A considerable increase of elastase levels after treatment was observed, whereas lactoferrin levels did not change. The percentage of patients with elevated elastase levels was significantly correlated with the degree of side effects. These findings suggest that neutrophil activation may be involved in the development of adverse reactions in these patients.