A neonatal care map based on gestational age

Care maps have been used successfully in the adult population. To evaluate the use of these patient care models in the neonatal population, one Level III NICU compared data on 146 infants who ranged in gestational age from 24 to 33 weeks. Nine clinical benchmarks were identified as serving to define the infant's progress. These nine benchmarks were back to birth weight, extubation, discontinuation of hyperalimentation, discontinuation of NCPAP, feeding trial via orogastric tube, weaned to open crib, discontinuation of oxygen, full oral feedings, and discharge home. Gestational age was consistently observed to be the dominant determinant of the infant's readiness to achieve these physiologic tasks. The result of this project is a neonatal care map, based on gestational age. This care map outlines the expected treatment and response of the neonatal patient. It serves as a guide for both clinicians and families.     

Strain gauge plethysmography and Doppler ultrasound in the measurement of limb blood flow

The maintenance of adequate oxygen delivery (DO2) and tissue uptake (VO2) has become central dogma in the management of the critically ill. However, these parameters are derived using gas tensions measured in mixed venous blood and may not reflect changes in regional blood flow. Therefore, it has become necessary to provide estimates of blood flow to specific organs and to evaluate the most adequate techniques available. In order to define the best means of assessing blood flow to the lower limb noninvasively in normal subjects, measurements of superficial femoral arterial blood flow using Doppler ultrasound (DU) and strain gauge plethysmography (SGP) were compared in 10 normal volunteers at rest and during exercise. To evaluate the effect of strain gauge positioning, results of measurements made under four different combinations of cuff/strain gauge placement were compared in 15 other volunteers. The correlation of the limb blood flow obtained using the two methods at rest and exercise was 0.57 and 0.62 and the limits of agreement (d +/- 2SD) were 0.40 +/- 2.49 and -0.86 +/- 5.22 ml 100 ml-1 tissue min-1 at rest and on exercise, respectively. Results obtained using SGP were more reproducible (Coef. repeat. 0.45 vs. 0.94 ml 100 ml-1 tissue min-1, for SGP and DU, respectively). The various combinations of cuff/strain gauge positioning showed a tendency to over-read when the latter was placed on the thigh, but were not significantly different (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Identification of homo- and heteromeric interactions between members of the breast carcinoma-associated D52 protein family using the yeast two-hybrid system

The hD52 gene was originally identified through its elevated expression level in human breast carcinoma. Cloning of D52 homologues from other species has indicated that D52 may play roles in calcium-mediated signal transduction and cell proliferation. Two human homologues of hD52, hD53 and hD54, have also been identified, demonstrating the existence of a novel gene/protein family. Since D52-like protein sequences are all predicted to contain a coiled-coil domain, we used the yeast two-hybrid system and glutathione S-transferase pull-down assays to investigate whether homo- and/or heteromeric interactions occur between D52-like proteins. Analyses of yeast strains co-transfected with paired D52-like constructs indicated that D52-like fusion proteins interact in homo- and heteromeric fashions through their predicted coiled-coil domains. Similarly, extensive two-hybrid screenings of a human breast carcinoma expression library identified hD53 and hD52 as potential interactors for both hD52 and hD53 baits. Thus, D52-like proteins appear to exert and/or regulate their activities through specific interactions with other D52-like proteins, which in turn may be intrinsic to potential roles of these molecules in controlling cell proliferation.     

Alterations in protein aggregation and degradation due to mild and severe missense mutations (A104D, R157N) in the human phenylalanine hydroxylase gene (PAH)

Although the importance of the father for the development of the child is well known and although an increased presence of the father in the family system is often demanded, processes of active shutting out the father occur. The deterioration of relation between father and child is not seen as a result of pathological male personality, but rather as a result of family or couple system. The special situation for counsellors of such cases is discussed.     

The pattern and tempo of the pubertal reaugmentation of open-loop pulsatile gonadotropin-releasing hormone release assessed indirectly in the male rhesus monkey (Macaca mulatta)

The purpose of this study was to determine the pattern and tempo of the open-loop reaugmentation of pulsatile GnRH release at the time of puberty in the male rhesus monkey. Episodic LH secretion from the in situ pituitary, in which responsiveness to GnRH was first heightened and subsequently sustained by priming with an i.v. intermittent infusion of the synthetic peptide, was used as an index of GnRH discharges. Ten male monkeys were castrated between 12 and 20 months of age, implanted with indwelling venous catheters, and housed in specialized cages that permitted remote access to the venous circulation with minimal restraint and without interfering with the light-dark cycle. Endogenous GnRH release was assessed by examining moment-to-moment changes in circulating LH concentrations measured at 12-min intervals for 7 h while GnRH priming was temporarily interrupted. A discharge of GnRH was inferred whenever a pulse of LH secretion was identified by a pulse detection program. Examination of nocturnal pulsatile GnRH release (1900-0200 h) was initiated as early as 14 months of age. GnRH release was assessed at 40-day intervals before 20 months of age and at 10-day intervals whenever possible thereafter. A simple algorithm was developed to identify the age at which a developmental increase in hypophysiotropic drive to the gonadotroph occurred. This was termed day zero and was considered to represent the age at which a pubertal mode of GnRH release was initiated. After the initiation of pubertal GnRH release was established, alternate nighttime and daytime (1100-1800 h) assessments of GnRH were performed. Before day zero, which was observed between 24 and 29 months of age, a stable, low frequency (<1 pulse/7 h), low amplitude pattern of pulsatile GnRH release was observed. Termination of the prepubertal mode of GnRH pulse generator activity was manifest as a relatively rapid nocturnal shift to a robust high-frequency pattern of activity. In some animals, the nocturnal acceleration to an adult GnRH pulse frequency (6-7 pulses/7 h) was attained within an epoch of only 30 days. Although initiation of the pubertal acceleration in nocturnal GnRH pulse generator activity seemed to be associated with an increase in GnRH pulse amplitude, it was not possible to decipher the subsequent developmental changes in this parameter. In some animals, the pattern of pulsatile GnRH release after the initiation of the pubertal acceleration was punctuated by periods of diminished activity, which seemed to be unrelated to the state of the pituitary-adrenal axis. These findings demonstrate that the neurobiological mechanisms that lead to the termination of the prepubertal mode of diminished GnRH release, and that therefore initiate the insidious process of puberty, have the potential to unfold with a surprisingly rapid time course. The extent to which the intrinsic tempo of the pubertal acceleration of pulsatile GnRH release in the agonadal situation is dampened by testicular feedback in the intact monkey remains to be established.     

Imputation for exposure histories with gaps, under an excess relative risk model

An Onchocerca volvulus expression library was differentially screened to identify a molecular marker distinguishing sowda (lichenified onchodermatitis) from other onchocerciasis forms. One clone, PG3, was recognized by pooled sera from patients with sowda, but not by pooled sera from patients with generalized onchocerciasis; it was not recognized by sera from patients with lymphatic filariasis or other helminth infections. The DNA of PG3 hybridized strongly with O. volvulus Eco RI-digested DNA, but not with DNA from Brugia spp., Trichinella spp., and humans. A weak reaction was observed with DNA from O. gibsoni and Acanthocheilonema viteae. The PG3 DNA sequence showed a high homology with both human and nematode collagens. Confirmation of the collagen-like nature of the sowda-specific PG3 product was obtained by amino terminal sequencing of the PG3 expression product, as well as by demonstrating its susceptibility to collagenase digestion. The characteristic recognition of the O. volvulus collagen specified by clone PG3 was confirmed by measuring antibody levels to the expressed product in individual sowda and generalized onchocerciasis sera, respectively. Identification of a nematode collagen antigen mainly recognized in sowda patients raises the possibility that this extreme form of dermatitis might arise through cross-reactivity between anti-O. volvulus collagen antibodies and human collagen. However, a relationship between the PG3 recognition by antibodies and the sowda pathogenesis could not be demonstrated.     

Thyroxine 5'-deiodination mediates norepinephrine-induced lipogenesis in dispersed brown adipocytes

In euthyroid rats, maximal sympathetic nervous system stimulation (e.g. during cold exposure) results in a 3- to 4-fold increase in brown adipose tissue lipogenesis, a response that is blunted in hypothyroid rats. To further investigate this phenomenon, the role of local type II 5'-deiodinase (5'-DII) was studied in freshly isolated brown adipocytes. In a typical experiment, 1.5 x 10(6) cells were incubated for up to 48 h in a water-saturated 5% CO2-95% O2 atmosphere. After incubation with medium alone or with different concentrations of T4, T3, and/or norepinephrine (NE), lipogenesis was studied by measuring 1) the rate of fatty acid synthesis as reflected by 3H2O incorporation into lipids and 2) the activity of key rate-limiting enzymes, i.e. acetyl coenzyme A carboxylase and malic enzyme, and the results are reported in terms of DNA content per tube. Lipogenesis decreased progressively over time (approximately 40%) when no additions were made to the incubation medium. T4 or T3 partially prevented that inhibition at physiological concentrations (65 x 10[-9] and 0.77 x 10[-9] M, respectively), whereas a receptor-saturating concentration of T3, (154 x 10[-9] M) doubled the lipogenesis rate. The addition of 10(-6) M NE inhibited lipogenesis acutely (approximately 50% by 12 h) and was followed by a progressive stimulation that reached approximately 2-fold by 48 h, but only in the presence of T4. Furthermore, NE did not attenuate T3 (154 x 10[-9] M)-induced lipogenesis. Both the inhibition and the stimulation of lipogenesis caused by NE showed a strong dose-response relationship within the range of 10(-11)-10(-5) M. The role of local 5'-DII was further tested by incubating brown adipocytes with 10(-6) M NE and T4 (65 x 10[-9] M) in the presence of 100 microM iopanoic acid, a potent inhibitor of 5'-DII. Although iopanoic acid did not affect the T3 stimulation of lipogenesis, it did block the approximately 2-fold stimulation of lipogenesis triggered by NE in the presence of T4, confirming the mediation of 5'-DII in this process. In conclusion, lipogenesis in brown adipose tissue is under complex hormonal control, with key roles played by NE, thyroid hormones, and local 5'-DII. As in other tissues, NE-generated signals acutely (12 h) inhibited lipogenesis. However, the presence of the 5'-DII generated enough T3 to stimulate lipogenesis and gradually reverse the short-lived NE-induced inhibition, leading to the 2- to 3-fold response observed at later time points.