Use of insulin-like growth factor I (IGF-I) and IGF-binding protein measurements to monitor feeding of premature infants

To determine whether peptides of the insulin-like growth factor (IGF) system might be useful indicators of nutritional adequacy in premature infants, we studied 50 premature (25-34 weeks gestation) infants prospectively to define the relationship between nutrient intake and serum concentrations of IGF-I, IGF-binding protein-2 (IGFBP-2), and IGFBP-3. Each infant was monitored for at least 2 weeks. Nutrient intake was quantified from daily logs; weight was determined daily, and measurements of IGF-I, IGFBP-2, and IGFBP-3 in serum were made twice weekly. Serum IGF-I correlated strongly with length of gestation, increasing 4.03 +/- 0.95 ng/mL for each additional week of gestation (P < 0.0001) and 0.36 +/- 0.07 ng/mL day each day since birth (P < 0.0001). A higher intake of calories increased IGF-I by 0.07 +/- 0.01 ng/mL for each calorie per kg ingested over the previous 3 days (P < 0.0001). IGF-I increased quadratically as protein intake increased. For each change of 1% in calories as protein squared, IGF-I increased 0.36 +/- 0.11 ng/mL (P < 0.0001). Serum IGFBP-3 concentrations also correlated with length of gestation, increasing 25.06 +/- 11.83 micrograms/L.wk (P = 0.035) and 4.14 +/- 1.33 micrograms/.day since birth (P = 0.003). Unlike IGF-I, variation in the amount of protein supplied did not change IGFBP-3. As calorie intake increased, IGFBP-3 increased by 0.54 +/- 0.17 microgram/L for each calorie per kg consumed over the previous 3 days (P = 0.0015). In contrast to IGF-I and IGFBP-3, IGFBP-2 declined as the length of gestation increased (56.12 +/- 16.92 ng/mL.week; P = 0.001) and with each additional day of life (7.57 +/- 2.44 ng/mL.day; P = 0.003). Dietary protein, the predominant regulator of IGFBP-2, caused a decrease of 33.22 +/- 9.00 ng/mL with each percent increase in dietary calories as protein (P < 0.0003). Calorie intake had less effect on IGFBP-2 than protein intake. These results indicate that each of the three peptides studied is regulated in premature infants by nutritional intake, and that their regulatory patterns are qualitatively similar to those observed in older individuals. Measurements of these peptides in premature infants may be useful indicators of nutritional status and adequacy of nutrient intake.     

Improving the accuracy of death certification

BACKGROUND: Population-based mortality statistics are derived from the information recorded on death certificates. This information is used for many important purposes, such as the development of public health programs and the allocation of health care resources. Although most physicians are confronted with the task of completing death certificates, many do not receive adequate training in this skill. Resulting inaccuracies in information undermine the quality of the data derived from death certificates. METHODS: An educational intervention was designed and implemented to improve internal medicine residents' accuracy in death certificate completion. A total of 229 death certificates (146 completed before and 83 completed after the intervention) were audited for major and minor errors, and the rates of errors before and after the intervention were compared. RESULTS: Major errors were identified on 32.9% of the death certificates completed before the intervention, a rate comparable to previously reported rates for internal medicine services in teaching hospitals. Following the intervention the major error rate decreased to 15.7% (p = 0.01). The reduction in the major error rate was accounted for by significant reductions in the rate of listing of mechanism of death without a legitimate underlying cause of death (15.8% v. 4.8%) (p = 0.01) and the rate of improper sequencing of death certificate information (15.8% v. 6.0%) (p = 0.03). INTERPRETATION: Errors are common in the completion of death certificates in the inpatient teaching hospital setting. The accuracy of death certification can be improved with the implementation of a simple educational intervention.     

Plant genetics: fast flowering

Bacillus cereus hemolysin III activity was tested in crude extracts, from Escherichia coli carrying the hly-III gene. It was concluded that hemolysin III is a pore-forming hemolysin with functional pore diameter of about 3-3.5 nm. Hemolysis occurs in at least three steps: (i) the temperature-dependent binding of the Hly-III monomers to the erythrocyte membrane; (ii) the temperature-dependent formation of the transmembrane oligomeric pore; (iii) the temperature-independent erythrocyte lysis.     

In utero transplantation of human fetal haemopoietic cells in NOD/SCID mice

BACKGROUND: Carotid angioplasty (CA) has been suggested to be a safer and more cost-effective alternative to carotid endarterectomy (CEA) in the management of symptomatic severe internal carotid artery (ICA) disease. METHODS: The study was conducted as a prospective consecutive randomized trial of CEA versus CA for symptomatic severe ICA disease in a university teaching hospital. All patients were assessed before and after surgery by a neurologist. The study consisted of 23 patients with focal carotid territory symptoms and severe ICA stenosis (> 70%) who were randomized to either CEA or CA. However, only 17 had received their allocated treatment before trial suspension. CEA with patching or CA with stenting were used as interventions. The main outcome measures were death or disabling or nondisabling stroke within 30 days. RESULTS: All 10 CEA operations proceeded without complication, but 5 of the 7 patients who underwent CA had a stroke (P=.0034), 3 of which were disabling at 30 days. CONCLUSIONS: After referral, the Data Monitoring Committee invoked the stopping rule and the trial was suspended. The investigators and the Ethics Committee subsequently concluded that the trial could not be restarted--even in an amended format-primarily because of problems with informed consent. We review many of the ethical dilemmas encountered in the performance of this study. If future trials do suggest a selected role for CA, it is essential that both the inclusion and the exclusion criteria are fully documented.     

The effects of cochlear hearing loss, age and sex on the auditory brainstem response

This study analyzed the effects of auditory impairment, age and sex on the auditory brainstem response (ABR) wave latencies. ABR wave I, wave V and I-V interval measures were extracted from the clinical records of 201 patients with cochlear hearing loss. Females had consistently earlier wave V latencies and shorter I-V intervals than males. No age effects were observed. Degree of impairment had a systematic effect on ABR wave latencies and I-V intervals. Wave I displayed latency extension with increasing levels of high-frequency hearing loss, whilst for wave V increases in latency were dependent upon both degree and slope of the hearing loss. Present results suggest that many of the previously reported sex differences and variable interactions seen for the ABR can be accounted for by differences in the underlying distribution of audiogram shapes within and between study populations. Different audiometric configurations were found to produce consistent differential effects on both wave I and wave V latency and thus influence the I-V interval. This study underlines the need to develop a more detailed model of impairment effects if correction factors are to be employed more effectively in ABR testing for retrocochlear pathology.     

Inhibition of mitogen-activated protein kinase kinase blocks T cell proliferation but does not induce or prevent anergy

Three mitogen-activated protein kinase pathways are up-regulated during the activation of T lymphocytes, the extracellular signal-regulated kinase (ERK), Jun NH2-terminal kinase, and p38 mitogen-activated protein kinase pathways. To examine the effects of blocking the ERK pathway on T cell activation, we used the inhibitor U0126, which has been shown to specifically block mitogen-activated protein kinase/ERK kinase (MEK), the kinase upstream of ERK. This compound inhibited T cell proliferation in response to antigenic stimulation or cross-linked anti-CD3 plus anti-CD28 Abs, but had no effect on IL-2-induced proliferation. The block in T cell proliferation was mediated by down-regulating IL-2 mRNA levels. Blocking Ag-induced proliferation by inhibiting MEK did not induce anergy, unlike treatments that block entry into the cell cycle following antigenic stimulation. Surprisingly, induction of anergy in T cells exposed to TCR cross-linking in the absence of costimulation was also not affected by blocking MEK, unlike cyclosporin A treatment that blocks anergy induction. These results suggest that inhibition of MEK prevents T cell proliferation in the short term, but does not cause any long-term effects on either T cell activation or induction of anergy. These findings may help determine the viability of using mitogen-activated protein kinase inhibitors as immune suppressants.