Mitogenic and protein synthetic activity of tissue repair cells: control by the postsurgical macrophage

It is well known that fibroblasts are a main source of extracellular matrix synthesis necessary for tissue repair. In addition, macrophages secrete products that are known to modulate synthesis of extracellular matrix. Accordingly, we studied the incorporation of [3H]thymidine, [3H]proline, and [35S]sulfate into macromolecules produced by fibroblasts recovered from the site of peritoneal tissue repair cultured with and without spent media from postsurgical peritoneal macrophages. Rabbits underwent resection and reanastomosis of their small intestines. Peritoneal exudative cells (PEC) were then collected on postsurgical day 5 and day 10 as well as from nonsurgical controls, separated by discontinuous Percoll gradient centrifugation, and cultured for 48 h. A second group of rabbits underwent peritoneal wall abrasion from which fibroblast tissue repair cells (TRC) were collected from the site of injury at postsurgical day 7 and maintained in culture for varying times. Incorporation of radiolabeled precursors into DNA, collagen, and sulfated proteoglycans was determined. Incorporation of [3H]thymidine and [3H]proline into untreated TRC gradually decreased with culture duration. Conversely, [35S]sulfate incorporation gradually increased during prolonged culture. Macrophage spent media increased the levels of [3H]thymidine incorporation by the TRC. [3H]Proline and [35S]sulfate incorporation into TRC were also stimulated by macrophage spent media. However, this stimulation may be due to the enhanced proliferation of TRC by macrophage spent media. In conclusion, tissue repair fibroblasts are activated for postsurgical repair at the site of injury by many factors including secretory products from postsurgical macrophages.     

Utility of the PFA-100 as a screening test of platelet function: an audit of haemostasis laboratories in Australia and New Zealand.

The PFA-100 is a relatively new laboratory instrument, first described in 1995. There have since been numerous studies assessing its utility as a screening tool for platelet dysfunction and/or von Willebrand's disease (VWD). The PFA-100 displays variable sensitivity to different types of platelet disorders, as well as to antiplatelet medication (e.g. aspirin), with similar caveats for monitoring of primary haemostasis-promoting therapies in platelet dysfunction. There is therefore considerable uncertainty regarding its utility within this context, and we have accordingly performed an audit of usage among participants of the Royal College of Pathologists of Australasia Quality Assurance Program. Of 105 laboratories surveyed, 40 responded that they performed platelet function testing, with 26 (65%) further indicating they utilized the PFA-100. We report a wide variety of laboratory usage among these users, including numbers of tests performed [annual median (range) = 270 (15-6000)], sources of requests (clinical sources and localities), testing criteria and follow-up action. Most tests were completed within 4 h of collection, as recommended by the manufacturer, and most tests were performed as a replacement, or as a preliminary screen of platelet function (i.e. classical aggregation). Most abnormal findings, however, were attributed to antiplatelet medication such as aspirin.     

Successful management of intra-abdominal hemorrhage in the presence of severe alcoholic liver disease with activated recombinant factor VII (rFVIIa; NovoSeven): a case report and review of the literature on approved and off-label use of rFVIIa.

A 37-year-old male with history of alcohol abuse presented to us with nausea, vomiting, and abdominal pain with ascites. He was diagnosed with alcoholic liver disease with coagulopathy and pancreatitis. During hospitalization, the patient developed intra-abdominal hemorrhage. He was treated with platelets, packed red blood cells and fresh frozen plasma without any improvement. Following this he was treated with activated recombinant factor VII (90 microg/kg), which resulted in normalization of the prothrombin time and the activated partial thromboplastin time and stabilization of hematocrit within a few hours. We review the current literature on the approved and off-label use of activated recombinant factor VII.     

Adequacy of hormone replacement therapy for osteoporosis prevention assessed by serum oestradiol measurement, and the degree of association with menopausal symptoms.

BACKGROUND: Patients on hormone replacement therapy (HRT) for osteoporosis prevention rather than menopausal symptom control may be asymptomatic, despite inadequate replacement and low serum oestradiol (E2) levels. In the primary health care setting, therapeutic monitoring of HRT is not carried out routinely so that patients with serum E2 levels inadequate to protect bone may be missed. AIM: To determine the proportion of women on transdermal E2 preparations with serum E2 levels insufficient to protect bone and to assess the value of a questionnaire-derived menopausal symptom score (MSS) for detecting these patients. METHOD: A cross-sectional analysis of 45 patients aged 35-70 years using transdermal E2 preparations obtained from a computer register of 14500 patients in a suburban practice. One blood sample was obtained from each patient at the time the MSS questionnaire was completed. Serum E2 concentration was measured using a fluoroimmunoassay and compared with the MSS. Levels below 150 pmol/l were considered to be insufficient to protect bone. The diagnostic accuracy of the MSS in screening for levels below 150 pmol/l was determined using receiver operating characteristic (ROC) curve analysis. RESULTS: The median (95% CI) serum E2 was 147 pmol/l (126-198 pmol/l) and levels were below 150 pmol/l in 24 out of 45 patients. There was no difference in the MSS (median, 95% CI) between those with serum E2 < 150 pmol/l (8.5, 5.0-17) and > or = 150 pmol/l (9.0, 5.0-14; P = 0.477). The degree of association between the serum E2 and the MSS, using the Spearman rank correlation coefficient, rs (95% CI) was small and not significant (-0.04, -0.34 to 0.26; P = 0.398). ROC curve analysis revealed an area under the curve (95% CI) of 0.51 (0.33-0.68). CONCLUSIONS: More than half the women were inadequately replaced to protect against osteoporosis. Furthermore, the MSS was of no value in screening for those with low serum E2 levels. Serum E2 levels should be monitored in women on HRT for osteoporosis prevention and the E2 dosage adjusted accordingly.     

Weight gain and height velocity in young children 1 year following bone marrow transplant: a single institution study.

The nutritional and growth effects on children following a bone marrow transplant (BMT) have not been well documented. The purpose of this study was to describe the growth patterns of young children during the first year following BMT. A retrospective chart review was used to examine the nutritional status of 25 young children, 1 to 6 years of age, who received an allogeneic BMT. Nutritional data were reviewed prior to BMT and at 3, 6, 9, and 12 months following BMT. The mean weight gain was 2.5 kg with a median weight gain of 2.3 kg (range, -1.2 to 9.4 kg). The mean height gain was 7 cm with a median height gain of 7.4 cm (range, 1.2 to 16.8 cm). Growth related to gender, age, and incidence of infection was similar to the overall average; however, children with graft-versus-host disease revealed poor weight and height gain. Nurses must learn to recognize patients at nutritional risk and intervene when necessary. More research is needed to address specific nutritional needs of the pediatric BMT patient.     

The emerging role of induced hypothermia in the management of acute stroke.

Current treatment of acute stroke remains unsatisfactory. This review presents experimental and clinical data which suggest that mild induced hypothermia could be a potent and practicable neuroprotective treatment of acute ischaemic stroke and intracerebral haemorrhage. Hypothermia, if proven to be safe, effective and widely practicable in patients with acute stroke, could have an enormous positive impact on reducing the burden of stroke worldwide. Critical issues that will need to be considered in a well designed randomised controlled trial of induced hypothermia in acute stroke patients are discussed.     

Glucocorticoid effects on rabbit fetal lung maturation in vivo: an ultrastructural morphometric study.

Maternal administration of glucocorticoids is known to stimulate fetal lung maturation. In the present study, we used microscopy and stereology to evaluate the morphological effects of maternal glucocorticoid treatment on rabbit fetal lung tissue. Betamethasone was administered to pregnant rabbits on days 25 and 26 of gestation at a dose of 0.2 mg/kg body weight. The animals were sacrificed on day 27 of gestation. Glucocorticoid treatment significantly increased the presumptive airspace in the fetal lung tissue but did not alter the relative proportion of epithelium, connective tissue, or vasculature in the tissue. In addition, glucocorticoid treatment significantly increased the proportion of type II cells in the prealveolar epithelium, increased the rate of phosphatidylcholine synthesis, and increased the content of the major surfactant-associated protein, SP-A, in the fetal lung tissue. We could detect no effect of betamethasone on lamellar body cross-sectional area, numerical density, or volume density within fetal lung type II cells. Glucocorticoid treatment of the pregnant doe caused a decrease in the volume density of intracellular glycogen and an increase in the volume density of mitochondria in fetal lung type II cells. Betamethasone treatment did not alter the distance between fetal lung epithelial cells and subadjacent connective tissue cells. However, glucocorticoid treatment increased the number of connective tissue foot processes that pierced the epithelial basal lamina. Thus, glucocorticoid treatment of the pregnant doe results in structural changes in the fetal lung tissue, an acceleration of some aspects of type II cell differentiation, and a concomitant increase in epithelial-mesenchymal interactions.     

Tritium dynamics in mice exposed to tritiated water and diet.

The contributions of tritiated water (3HHO) and dietary tritiated amino acids to the steady-state specific activities of tissue water tritium and organically bound tritium in mice were essentially independent and additive. Following exposure (56 d), organically bound tritium clearance was resolved into two distinct compartments. The first, with a half-life of 1-2 d, likely represented exchangeable organically bound tritium, and the second, with a half-life of 20-30 d, likely represented nonexchangeable organically bound tritium. Since organically bound tritium was cleared much more slowly than tissue water tritium, organically bound tritium was the principal determinant in estimated radiation doses to mice following exposure.