To stay or not to stay: are fears about shorter postnatal hospital stays justified?

Common concerns raised during a Ministerial Review of Birthing Services in Victoria, Australia about the potential detrimental effects of shorter hospital stays after birth were examined in a study of women's actual experiences of and opinions about their hospital stays. Just under one in four women left hospital within five days of the birth, with the greater majority staying five days or more. Satisfaction with length of stay was high in the sample, with 82% of women feeling their stay had been about right, 11% feeling it had been too long and only 7% of women feeling their stay had been too short. A number of the concerns about the consequences of shorter lengths of stay were not borne out. Women who left hospital earlier than the traditional 5-7 day stay were not less likely to breast feed, nor were they more likely to be depressed 8-9 months after the birth. They were also much more likely to feel confident about looking after their baby when they went home than women who stayed five days or more. Implications for further research and for policy development concerning length of stay are considered.     

Autophagic degradation of protein generates a pool of ferric iron required for the killing of cultured hepatocytes by an oxidative stress

Pretreatment of cultured hepatocytes with the ferric iron chelator deferoxamine prevents the killing of the cells by tert-butyl hydroperoxide (TBHP). Incubation of the deferoxamine-pretreated hepatocytes in a serum-free medium containing only 0.25 nM iron restored the sensitivity of the cells to TBHP within 4 to 6 hr. An amino acid-free medium accelerated the restoration of sensitivity in parallel with an enhanced rate of degradation of 14C-prelabeled protein. By contrast, inhibitors of the autophagic degradation of protein, including chymostatin, 3-methyladenine, benzyl alcohol, colchicine, oligomycin, and methylamine, inhibited the restoration of sensitivity of deferoxamine-treated hepatocytes to TBHP in parallel with their inhibition of protein degradation. With chymostatin, 3-methyladenine, benzyl alcohol, and colchicine, there was a parallel dose dependency of both the inhibition of protein turnover and the inhibition of the restoration of sensitivity to TBHP. Ascorbic acid, known to specifically retard the autophagic degradation of ferritin, inhibited the restoration of sensitivity to TBHP without effect on the general rate of protein turnover. None of the agents studied had any protective effect on the toxicity of TBHP for hepatocytes that were not pretreated with deferoxamine. These data indicate that the autophagic degradation of protein generates a pool of ferric iron required for the killing of cultured hepatocytes by TBHP.     

The kidney in hypertensive pregnancies--victim and villain.

Many changes in renal function occur in normal pregnancy. Without a proper understanding of these changes, routine clinical investigations may easily be misinterpreted. Women with preeclampsia have further alterations in renal function and, in occasional cases, develop acute renal failure. Understanding of abnormal renal physiology and hormonal changes in these women allows the clinician to interpret biochemical tests appropriately and make proper use of vasodilator therapy with careful attention to volume homeostasis. Women who undertake pregnancy with a primary renal disease, most commonly glomerulonephritis or reflux nephropathy, have a higher risk of adverse fetal and maternal outcomes. Awareness of these risks provides a basis for proper preconceptual counseling, as well as careful monitoring of maternal blood pressure and renal function and fetal growth during such pregnancies. These strategies will optimize the chances of a successful pregnancy outcome for both mother and baby.     

The cigarette controversy.

This study examines the history of the cigarette controversy using the tobacco documents as a roadmap to explore the following four questions: (a) What did tobacco companies know about the health risks of smoking and when did they know it? (b) What evidence is there that tobacco companies conspired to deliberately mislead the public about the health risks of smoking? (c) How were scientists involved in the cigarette controversy? (d) Have tobacco companies changed the way they do business since signing the 1998 Master Settlement Agreement? The tobacco companies knew and for most part accepted the evidence that cigarette smoking was a cause of cancer by the late 1950s. The documents also reveal that the tobacco companies helped manufacture the smoking controversy by funding scientific research that was intended to obfuscate and prolong the debate about smoking and health. Today, the tobacco companies acknowledge that smoking is a cause of disease, but they have not materially altered the way they do business. In our opinion, it is not sufficient for the tobacco industry to merely concede the obvious point that smoking is a cause of disease when it is evident that decades of misinformation has resulted in a public that is massively ignorant about the risks of smoking low-tar cigarettes, nicotine addiction, and secondhand smoke exposure. Public education efforts are still needed to correct these misperceptions along with government oversight to ensure that the industry is not permitted to mislead the public further. If the past 50 years have taught us anything, it is that the tobacco industry cannot be trusted to put the public's interest above their profits no matter what they say.     

Reversible inhibitors of the gastric (H+/K+)-ATPase. 3. 3-substituted-4-(phenylamino)quinolines.

Previously, gastric (H+/K+)-ATPase inhibitors such as 2 have been prepared as analogues of 1a on the presumption that the 3-carbethoxy substituent plays a key role in establishing the orientation of the 4-arylamino group. In this paper we explore further the contribution made to activity by the quinoline 3-substituent. We show that, for compounds bearing such a substituent, only a particular combination of properties provides high activity, both in vitro and as inhibitors of gastric acid secretion in vivo. The ability of the substituent to affect activity by restricting rotation about the Cquin-N bond through a combination of both a pi-electron withdrawal and hydrogen bonding is supported by the current study. However, high activity is only achieved if the effect of this group on the quinoline pK(a) is kept to a minimum. 3-Acyl substituents provide an optimum combination of electronic properties. From this series, compound 17c (SK&F 96067) was shown to be a potent inhibitor of histamine-stimulated gastric acid secretion after oral dosing in the Heidenhain pouch dog and was selected for further development and evaluation in man.     

The effect of monoclonal antibodies to calcitonin gene-related peptide (CGRP) on CGRP-induced vasodilatation in pig coronary artery rings.

1. The modification of the vasodilator effect of calcitonin gene-related peptide (CGRP) by a panel of monoclonal antibodies (MAbs), which map to discrete epitopes on the CGRP molecule, was investigated in pig coronary artery rings (PCA). The preparations were pre-constricted with acetylcholine (3 x 10(-7) M) and concentration-response curves to CGRP (2 x 10(-10)-2.56 x 10(-8) M) were obtained in the presence or absence of each MAb. 2. CGRP caused a concentration-dependent relaxation of PCAs which reached a maximum (98.2 +/- 4.8%, n = 25) at 1.28 x 10(-8) M and gave an EC50 of 3.8 +/- 0.8 x 10(-9) M. 3. Two MAbs which map to the N-terminal, CN1 and CRA3, did not affect the CGRP response whilst a third, CRA5, significantly inhibited its effect. 4. The C-terminal MAb, CRA2, did not modify the CGRP response whilst, in contrast, CB3 (C-terminal) potentiated its effect. A similar augmentation of the CGRP-induced vasodilatation was seen in the presence of the middle-region MAb, CRA8. 5. These results suggest that regional specific MAbs can modify the vasodilator effect of CGRP causing either inhibition (CRA5, N-terminal) or potentiation (CB3, C-terminal; CRA8, middle region).     

Rabbits produce SLE-like anti-RNA polymerase I and anti-DNA autoantibodies in responses to immunization with either human or murine SLE anti-DNA antibodies.

Anti-DNA and anti-DNA polymerase I (RPI) autoantibody responses are symptoms of systemic lupus erythematosus (SLE). To investigate the relationship between these antibodies (Ab), rabbits were immunized with one of the following preparations: human SLE anti-DNA Ab; human SLE anti-DNA IgG; normal human anti-DNA Ab; human Grave's disease anti-DNA Ab; murine SLE anti-DNA Ab or anti-DNA IgG Fab; various normal human, murine, or rabbit IgG preparations; or complete Freund's adjuvant (CFA), alone. All of the animals immunized with anti-DNA Ab (n = 14) generated Ab reactive in radioimmunoassay with: ssDNA, dsDNA, RPI, the soluble fraction of rabbit liver crude nuclear extract, and the immunogen. Induced rabbit anti-DNA Ab in turn induced these responses in a different rabbit: a rabbit immunized with rabbit anti-DNA IgG Ab which had been previously induced by immunization with human anti-DNA Ab, produced Ab reactive with ssDNA, dsDNA, RPI, and the soluble fraction of rabbit liver nuclear extract. Although an individual animal's antisera reacted consistently over the course of immunization with the same individual RPI subunit(s), antisera from different animals reacted with different subunits of the 9-subunit RPI complex in Western blot analyses: 190 kD (n = 6); 120 kD (n = 1); 62 kD (n = 4); 45 kD (n = 2); and, no reactivity (n = 2). In contrast, animals immunized with normal IgG or CFA produced responses only against the immunogen. Together, these data suggest that anti-DNA and anti-RPI responses are connected through an autoimmune network in SLE.     

Determinants of dietary intake during childhood diarrhea and implications for appropriate nutritional therapy

Diarrheal diseases have a well recognized negative effect on children's growth, probably due in part to reduced dietary intake during illness. Previous studies have shown that the effects of diarrhea on dietary intake are greater among hospitalized children than among those observed in their homes. Breast milk intake does not change during diarrhea, however, so breast-fed children are less likely to reduce their total energy and nutrient intakes. Recent analyses of clinical studies found that acidosis and dehydration were most closely associated with reduced dietary intake of hospitalized patients. The implications of these and other studies for the dietary management of patients during and after diarrhea are discussed.