Effects of decreased insulin-like growth factor-1 stimulation on hypoxia inducible factor 1-α protein synthesis and function during cutaneous repair in diabetic mice

Insulin-like growth factor-1 (Igf-1), a critical mediator of tissue repair, is significantly decreased in diabetic wounds. Furthermore, decreased levels of hypoxia-inducible factor 1-alpha (Hif-1alpha) and its target genes are also associated with impaired wound healing in diabetic mice. The aim of our study was to examine whether the reduced levels of Igf-1 are responsible for the reduction in Hif-1alpha protein synthesis and activity in diabetic wounds. We provide evidence that Igf-1 regulates Hif-1alpha protein synthesis and activity during wound repair. In addition, Igf-1 stimulated phosphytidylinositol 3-kinase activity in diabetic fibroblasts, which, in turn, increased activation of the translational regulatory protein, p70 S6 kinase. Moreover, improved healing of diabetic wounds by addition of recombinant IGF-1 protein was associated with an increase in Hif-1alpha protein synthesis and function in vivo.     

Sleep length and quality,sleepiness and urinary melatonin among healthy Danish nurses with shift work during work and leisure time

Background  

Sleep problems are common effects of shift work. The aim of the present study was to evaluate how different types of shift affect sleep and sleepiness, and to relate sleepiness to urinary 6-sulfatoxymelatonin.     

Once-daily gentamicin dosing for the preterm and term newborn: proposal for a simple regimen that achieves target levels.

OBJECTIVE: Based on recent safety and efficacy data, combined with the known pharmacokinetic parameters of aminoglycosides in the newborn, once-daily gentamicin should be preferable to the many other dosing regimens currently in use. Although there are growing data to support its use in term newborns, experience with preterm infants is more limited. In our Neonatal Intensive Care Unit, we experienced difficulties regarding complicated dosing regimens, actual dosing errors, and the tendency to check trough and peak levels around the third dose for infants receiving only a 48 hour course. Therefore, we conducted a quality improvement initiative in which we developed and tested a clinical practice guideline for the use of once-daily gentamicin for preterm and term infants that we hoped would yield trough and peak levels in our target range. METHODS: We combined a review of the published English language literature with pharmacokinetic analysis of our own data prior to initiation of this new regimen to design the following dosing regimen: <35 weeks gestation: 3 mg/kg q 24 hours, > or =35 weeks gestation: 4 mg/kg q 24 hours. Our goal serum levels were a trough < or =2 microg/ml and a peak between 6 and 12 microg/ml. We collected and analyzed trough and peak levels from all infants receiving this dosing regimen in the first week of life for at least 72 hours between 3/1/99 and 12/31/00. RESULTS: In total, 214 babies met our inclusion criteria, 75 of whom were <35 weeks gestation. 100% of babies of all gestational ages had a nontoxic trough level. For infants <35 weeks gestation, 79% had a therapeutic peak level, with a mean value of 6.8 microg/ml. For infants of at least 35 weeks gestation, 93% had a therapeutic peak level, with a mean value of 8.4 microg/ml. 92% of nontherapeutic peaks were too low. CONCLUSION: This study of once-daily gentamicin represents the largest sample size of pre-term infants published to date. The proposed regimen is simple and yields a high proportion of desirable levels. We recommend it for use in preterm and term newborns.     

Mathematically directed single-cut osteotomy for correction of tibial malunion

In 1986 and 1987, four patients with tibial malunion involving both angular and torsional misalignment underwent surgical correction by a single-cut technique based on a mathematical model of long bone deformity. The technique involved a single surgical cut, followed by rotation of the two fragments along the osteotomy plane. The orientation of the osteotomy is based on a computer-assisted design. The deformity is measured on radiographs, computed tomography, and clinical exam and is then plotted on graphs to find the osteotomy orientation. The deformity involved varus and extension in four cases, internal rotation in 2, and external rotation in two. The deformities ranged from 9 to 26 degrees. The cutting angle of the osteotomy ranged from 50 to 66 degrees as measured from the transverse plane. Actual lengthening of 1 cm and functional lengthening over 1.5 cm was obtained without the use of bone graft. As no wedge of bone was removed, all corrected bones were easily suited to rigid internal fixation across the cut surface. In all cases, the desired correction was obtained within measurable error, and union was obtained with minimal immobilization. There were no soft tissue or joint contractures, and no neurovascular complications. In one patient, who had had four prior surgical procedures on the involved limb, an infection developed 6 weeks postoperatively that required debridement and delayed primary closure. As the technique involves only one cut, no wedge of bone is removed, no shortening occurs, and the osteotomy is highly suitable for rigid internal fixation. The described technique is the first to integrate in a precise way the correction of torsion with the correction of angular deformity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibitory effects of amitriptyline on the stimulation-induced Ca2+ increase in parotid acini

The present study demonstrates the effects of the antidepressant, amitriptyline, and the acetylcholine antagonist, atropine, on the stimulation-induced rise in cytosolic, free Ca2+ (Cai2+). The changes in Cai2+ of collagenase-isolated rat parotid acini were measured by means of the Ca2(+)-sensitive dye, fura-2. It was found that stimulation by carbachol resulted in a maximal increase of 582 +/- 34 nM (mean +/- S.E.) in Cai2+ with a ks of 5.8 +/- 1.3 microM. Adrenaline caused a rise of 380 +/- 22 nM in Cai2+ with a ks of 0.5 +/- 0.2 microM. Amitriptyline and atropine were found to inhibit the carbachol-induced rise in Cai2+ with dissociation constants (kI) of 105 and 1.25 nM, respectively, in the absence of agonist. The adrenergic-induced rise in Cai2+ was inhibited by amitriptyline with a kI of 45 nM. Amitriptyline was found to inhibit both receptor classes by a competitive or mixed type of inhibition. Similarly, atropine exerted the same type of inhibition on the acetylcholine receptor. Amitriptyline and atropine were found to be mutually exclusive for competing for substrate binding on the receptor. These findings are consistent with a common binding site for amitriptyline and atropine on the acetylcholine receptor, possibly in close proximity with, but different from the substrate binding site. The stimulation-induced cell shrinkage evoked by the loss of electrolytes and water from the acini was measured by a 90 degree light scattering signal. It was found that this method makes possible the detection of autonomic side-effects of antidepressants on acini suspended in protein-containing media.     

Internal fixation of children's fractures of the lower extremity

Lower grade fractures are by definition stable and almost always treated with casting or functional splinting. The best kind of fixation for the higher grade fractures, however, differs between adults and children. Appropriate treatments are discussed, and case-study illustrations are provided. Background on the anatomy of the tibia and femur is included.     

Digital movement analysis,a new objective method of measuring tardive dyskinesia and drug-induced parkinsonian tremor: acceptability,reliability and validity

Digital movment analysis (DMA) is a new instrumental approach to assessing oral tardive dyskinesia (TD) by means of digital image processing of a video signal, tracking five paper dots placed around the patient's mouth. A total of 40 schizophrenic patients, 30 with and 10 without TD, were examined twice (with a 3-month interval) with this new device. The patients were further examined with two TD rating scales: the St. Hans Rating Scale for extrapyramidal syndromes (SHRS) and the Abnormal Involuntary Movement Scale (AIMS).The schizophrenic patients accepted the instrumental assessment without any anxiety or resistance. The internal relibility of the apparatus was high, with correlation coefficients of 0.80–0.99. The DMA TD values correlated with the SHRS and AIMS scores with correlation coefficients of 0.48–0.73 indicating an acceptable, although not strong, concurrent validity. Fluctuations occurred from the first to the second examination independent of medication. For these fluctuations no correlation was found between DMA values and rating scores. Finally, the DMA device was able to detect perioral tremor as a sign of parkinsonism.It has been concluded that DMA is a useful supplement to classical TD rating, although further validity evaluation is warranted.     

Antibody levels against Streptococcus pneumoniae and Haemophilus influenzae type b in a population of splenectomized individuals with varying vaccination status.

In order to determine antibody levels against Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae type b (Hib) in a population of splenectomized subjects, 561 persons in a Danish county, splenectomized between 1984 and 1993 were identified. Two hundred and thirty-five were alive and 149 participated in the study. Each person donated a blood sample for antibody determination by ELISA. Though vaccine coverage among the 149 persons was 91% only 52% had ''protective'' levels of pneumococcal antibodies. Despite recommendations for regular follow-up on pneumococcal antibody levels this had only been carried out in 4% of the subjects. Splenectomized subjects who needed pneumococcal revaccination were significantly more likely to have received their initial vaccination less than 14 days before or after splenectomy, as recommended, than those not requiring revaccination. Therefore, the timing of initial pneumococcal vaccination in relation to splenectomy seems to be important. All persons had Hib antibody levels higher than 0.15 microgram/ml and 60% had levels higher than 1 microgram/ml, which are the levels thought to provide short term and long term protection, respectively. In total, 37% of the 149 persons tested had pneumococcal and Hib antibody levels thought to correlate with protection from serious infections.