Non-invasive ventilation for children with acute respiratory failure in the developing world: literature review and an implementation example.

Over 2 million children die of acute respiratory infection every year, with around 98% of these deaths occurring in developing countries. Depending upon the clinical status of the patient, supplemental oxygen is usually the first line therapy. However this often proves inadequate for acute respiratory failure (ARF), in which case intubation and mechanical positive pressure ventilation are required. Adult intensive care successfully introduced non-invasive positive pressure ventilation (NIPPV) to treat ARF over a decade ago. This experience, coupled with the use of NIPPV in children with chronic respiratory insufficiency, has led to increasing use of NIPPV to treat ARF in paediatric populations. NIPPV can have similar or improved outcomes to IPPV, but with fewer complications. However there are no controlled trials of its use in children, and most data come from observational studies and retrospective reviews. In a developing world setting, where mortality from ARF is high and the risks of intubation are great and often not feasible, NIPPV can be a simple and cost-effective way to treat these patients. Its implementation in rural Northern Ghana shows NIPPV for ARF can be delivered safely with minimal training, and appears to impact significantly on mortality in those under 5 years.

Selective failure of androgens to regulate follicle stimulating hormone beta messenger ribonucleic acid levels in the male rat.

FSH beta, as well as LH beta, and alpha-subunit mRNA levels were examined in the pituitary glands of male rats after sex steroid replacement at various times (7, 28, or 90 days) after orchiectomy. Testosterone propionate, dihydrotestosterone propionate, or 17 beta-estradiol benzoate (E) were administered daily for 7 days before killing, to assess the role of different gonadal steroids on gonadotropin subunit mRNA levels. Subunit mRNAs were determined by blot hybridization using rat FSH beta genomic DNA, and alpha and LH beta cDNAs. At all time points, alpha and LH beta mRNAs increased after gonadectomy and fell toward normal levels with either androgen or estrogen replacement. FSH beta mRNA levels increased variably postcastration: 4-fold at 7 days, 2-fold at 28 days, and 4- to 5-fold at 90 days. Although E replacement uniformly suppressed FSH beta mRNAs, neither testosterone propionate nor dihydrotestosterone propionate administration suppressed FSH beta mRNA levels at any time point after orchiectomy. These data demonstrate that there is a relative lack of negative regulation of FSH beta mRNA levels by androgens in a paradigm in which E administration results in marked negative regulation of FSH beta mRNA levels. Thus, in the male rat, estrogens negatively regulate all three gonadotropin subunit mRNA levels while androgens negative regulate LH beta and alpha-subunit but fail to suppress FSH beta mRNAs.

Effects of gonadal steroids on clearance of growth hormone at steady state in the rat.

Gonadal steroids have been implicated in the modulation of GH secretory patterns in the rat. We have studied the effects of testosterone (T) or estradiol (E2) on the steady state clearance (Clss) and plasma half-life (t1/2) of GH in male and female rats (n = 4-6/group). A femoral and a jugular cannula were surgically implanted into adult Sprague-Dawley rats. At the time of cannulation some rats were orchidectomized, and a Silastic capsule containing E2, T, or nothing was implanted sc. After recovery from surgery, either purified rat GH or a crude extract of rat pituitary was infused iv to attain steady state plasma GH concentrations. Blood samples were taken every 30 min for 4 h during the infusion, and nine samples were taken at 2.5-min intervals immediately after stopping the infusion. The mean Clss for GH in female rats were significantly (P less than or equal to 0.001) less than that in males, whereas the t1/2 did not differ between the two groups. Neither the Clss nor the t1/2 was affected by castration in males or females. The Clss of GH in E2-treated castrated males was significantly less (P less than 0.001) than that for intact males, but the t1/2 did not differ between the two groups. The Clss for GH was greater in T-treated ovariectomized rats than in intact females, but the t1/2 did not differ with T treatment. These results suggest that 1) the Clss for GH is lower in female rats than in males; 2) 4 weeks of gonadectomy has no effect on the Clss in males or females; 3) under experimental conditions, E2 decreases and T increases the Clss for GH; and 4) the t1/2 for GH is not different in males or females. The steroid-induced changes in Clss in the absence of detectable effects on t1/2 suggest that factors affecting the volume of distribution at steady state (i.e. plasma GH-binding proteins or GH heterogeneity) are involved in the effects of gonadal steroids on GH clearance in the rat.

Binding of Xenopus oocyte masking proteins to mRNA sequences.

It has been shown previously that maternal mRNA, synthesized and stored in growing oocytes, is stabilized and blocked from translation through various mechanisms including restricted polyadenylation and the binding of proteins to 3' regulatory elements. In addition to binding sequence-specific proteins, the bulk of stored mRNA is packaged with a set of 'masking' proteins, the most abundant of which are the phosphoproteins pp56 and pp60. In this report these proteins are shown to be bound to heterogeneous mRNA sequences and not to the 3' poly(A) tract. Crosslinking studies demonstrate that all of the pp56/60 present makes direct contact with the RNA. In vitro binding studies confirm that pp56/60 interact with single-stranded RNA of heterogeneous sequence, such as occurring in the maternal mRNA encoding cyclin B1. However, binding is equally effective to capped and polyadenylated cyclin mRNA, to truncated mRNA lacking 5' and 3' non-coding regions and even to the antisense sequence. Lengths of 70-80 nucleotides are protected from ribonuclease digestion after protein binding. Although no extended binding motif could be detected, binding does appear to have some specificity in that it is not competed out by 100-fold excess of double-stranded RNA, transfer RNA, poly(A) and various other homopolymers and heteropolymers. The sequence which competes most efficiently is the mixed polypyrimidine, poly(C,U). Crosslinking of RNA-protein complexes, followed by ribonuclease digestion, suggests that the arrangement of proteins on RNA is as dimers. Dimerization appears to be stabilized by phosphorylation of pp56/60. These results are discussed in terms of the known structures of pp56/60.

Endotoxic shock elicits greater endorphin secretion than hemorrhage.

Opiopeptides may contribute to the pathophysiology of both endotoxic and hemorrhagic shock. To determine if endorphin secretion is similar in both types of shock, we divided 25 sheep into three groups: a saline control group (n = 10), an endotoxin-treated group (n = 9), and a hemorrhage group (n = 6). Each sheep had baseline determinations of mean arterial pressure (MAP) and plasma levels of beta-endorphin-like immunoreactivity (iB-EP). Experimental animals either received endotoxin (450 ng/kg intravenous) or underwent withdrawal of blood volume sufficient to diminish MAP by approximately one-third of baseline values. MAP and iB-EP levels were determined every 15 minutes thereafter for 5 hours. Individual data were averaged within each group and then compared between groups using analysis of variance. Both the endotoxin- and hemorrhage-treated groups showed a significant fall in MAP, which was significantly lower in the hemorrhage group than the endotoxin group. Endotoxin-treated animals displayed a mean peak iB-EP level 1,550% above baseline as compared to a mean peak iB-EP level of only 201% above baseline in the hemorrhage-treated group, despite a significantly greater degree of hypotension in the latter group; this difference in peak iB-EP response was significant. Mean peak iB-EP levels coincided with mean trough MAP values in the endotoxin-treated group while the mean peak iB-EP lagged the onset of mean trough MAP in the hemorrhage group. These results demonstrate that iB-EP secretory patterns differ in endotoxic versus hemorrhagic shock and suggest that distinct mechanisms of opiopeptide secretion accompany the two shock states.

Divergent regulation of gonadotropin subunit mRNA levels by androgens in the female rat.

To examine the effects of gonadal steroids on the pretranslational regulation of the gonadotropin subunits in the female, adult female rats, beginning 7 or 28 days after ovariectomy, received daily injections of testosterone propionate (T), dihydrotestosterone propionate (D), or estradiol benzoate (E) for 7 days. Intact cycling females and ovariectomized rats that received vehicle served as controls. Serum was obtained for LH and FSH levels to assess changes in gonadotropin secretion. Total RNA from individual rats was recovered and analyzed by blot hybridization with specific radiolabeled cDNA probes for the alpha, LH beta, and FSH beta subunits. Autoradiographic bands were quantitated and standardized to mRNA levels in the intact animals. Ovariectomy resulted in a rise in serum gonadotropin levels and all three gonadotropin subunit mRNA levels. Estrogen replacement resulted in suppression of alpha, LH beta, and FSH beta mRNAs whether given at 7 or 28 days after ovariectomy. In contrast, whereas androgen replacement decreased alpha and LH beta mRNAs, D or T did not consistently suppress FSH beta mRNAs. We conclude that chronic estrogen administration to the castrated female rat uniformly suppresses all three gonadotropin subunit mRNA levels. In female rats, as in male rats, chronic androgen administration fails to negatively regulate FSH beta mRNAs.