Acute asthma, salbutamol and hyperglycaemia

The effects of frequent high-dose nebulized salbutamol on plasma glucose concentrations were studied in 12 children (mean age 60 months) with acute severe asthma. There was a significant difference between mean initial glucose levels and peak levels. We conclude that hyperglycaemia can be produced in children as a result of nebulized salbutamol.     

'Sheltered disruption' of Neurospora crassa MOM22, an essential component of the mitochondrial protein import complex

MOM22 is a component of the protein import complex of the mitochondrial outer membrane of Neurospora crassa. Using the newly developed procedure of 'sheltered disruption', we created a heterokaryotic strain harboring two nuclei, one with a null allele of the mom-22 gene and the other with a wild-type allele. Homokaryons bearing the mom-22 disruption could not be isolated, suggesting that mom-22 is an essential gene. The mutant nucleus can be forced to predominate in the heterokaryon through the use of specific nutritional and inhibitor resistance markers. Cultivation of the heterokaryon under conditions favoring the mutant nucleus resulted in selective depletion of MOM22. MOM22-depleted cells did not grow and contained mitochondria with an altered morphology and protein composition. Protein import into isolated, MOM22-depleted mitochondria was abolished for most precursor proteins destined for all subcompartments. In contrast, precursors of MOM19, MOM22 and MOM72 became inserted normally into the outer membrane, defining a novel MOM22-independent import pathway which remained intact in mutant mitochondria. Furthermore, the specific binding of the ADP/ATP carrier to the outer membrane was unaffected, but subsequent transport across the outer membrane did not occur. Our data show that MOM22 is an essential component of Neurospora cells specifically required for the biogenesis of mitochondria.     

Lung function measurement in general practice: a comparison of the Escort spirometer with the Micromed turbine spirometer and the mini-Wright peak flow meter

It is important that new types of spirometer for widespread clinical use are pragmatically evaluated in primary care. This study compared measurements taken by a new portable Fleisch pneumotachograph spirometer (known as the Escort) with those of the commonly used mini-Wright peak flow meter and the Micromed Pocket turbine spirometer. A pragmatic study was conducted in two phases during routine surgeries at Aldermoor Health Centre, Southampton. Phase I compared the new spirometer with the mini-Wright peak flow meter and Phase 2 compared the new spirometer and the turbine spirometer. One hundred patients aged 5-88 years (56 patients with a history of chronic respiratory complaints and 44 patients without) entered Phase 1, and 100 patients aged 6-82 years (62 patients with a history of chronic respiratory complaints and 38 patients without) entered Phase 2. Each patient contributed only once to each phase, but some entered both phases on separate occasions. Ninety-five percent limits of agreement (mean +/- SD) were wide for all comparisons. Graphical plots revealed trends towards higher Escort values as mean values rose compared with both mini-Wright and turbine readings for peak expiratory flow rate and forced expiratory volume in one second. Possible over-reading of peak expiratory flow rate with the mini-Wright meter at low mean values was also seen. Readings taken with these different types of meter cannot be interchanged with confidence in clinical practice. The clinical significance of the theoretically more accurate measures of lung function produced with the new meter, and indeed of spirometry itself, needs further investigation.     

Recent developments of collagen-based materials for medical applications and drug delivery systems

In this review, an attempt was made to summarize some of the recent developments in the application of collagen as a biomaterial and in drug delivery systems. The main applications covered include: collagen for burn/wound cover dressings; osteogenic and bone filling materials; antithrombogenic surfaces; and immobilization of therapeutic enzymes. Recently, collagen used as a carrier for drug delivery has attracted many researchers throughout the world. The use of collagen for various drug delivery systems has also been reviewed in this article. Collagen-based drug delivery systems include: injectable microspheres based on gelatin (degraded form of collagen); implantable collagen-synthetic polymer hydrogels; interpenetrating networks of collagen; and synthetic polymers collagen membranes for ophthalmic delivery. Recent efforts to use collagen-liposomal composites for controlled drug delivery, as well as collagen as controlling membranes for transdermal delivery, were also reviewed. In this review, the main emphasis was on the work done in our laboratory.     

Formulaic methods of estimating calorie requirements in mechanically ventilated obese patients: a reappraisal

We reviewed 410 cases, 365 males and 45 females, mean age 64 years, of inguinal and femoral hernia, from 1/1/1991 to 31/12/1994, repaired with Lichtenstein and Trabucco techniques. Recurrent hernias repaired were 36 (8,8%). Local anesthesia was used in 82% and follow-up has ranged from 6 months to 4 years. The meshes used are made with a single layer of polipropylene and the Trabucco plugs T1 were made by hand at the operating table. In our experience these two techniques are simple, but is very important, before application of the mesh, a correct dissection of inguinal region. We made a complete excision of cremasteric fibers preservig, if possible, the genital branch of the genitofemoral nerve. The transversalis fascia is introflected and sutured in direct hernia repair or when there are a loss of tissues. The preliminary results obtained with the "tension free" hernioplasty are satisfying. The most important complications were 9 hematomas and an important and persistent inguinal neuralgia in 1 case. There were no recurrences, but we must considered the short follow-up period.     

Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions

Cytotoxic T lymphocyte (CTL) activation requires specific T cell receptor (TCR)-class I major histocompatibility complex (MHC) antigen complex interactions as well as the participation of coreceptor or accessory molecules on the surface of CTL. CD8 can serve as a coreceptor in that it binds to the same MHC class I molecules as the TCR to facilitate efficient TCR signaling. In addition, CD8 can be "activated" by TCR stimulation to bind to class I molecules with high avidity, including class I not recognized by the TCR as antigenic complexes (non-antigen [Ag] class I), to augment CTL responses and thus serve an accessory molecule function. A Glu/Asp227-->Lys substitution in the class I alpha 3 domain acidic loop abrogates lysis of target cells expressing these mutant molecules by alloreactive CD8-dependent CTL. Lack of response is attributed to the destruction of the CD8 binding site in the alpha 3 domain which is likely to disrupt CD8 coreceptor function. The relative importance of the class I alpha 3 domain acidic loop Glu227 in coreceptor as opposed to accessory functions of CD8 is unclear. To address this issue, we examined CTL adhesion and degranulation in response to immobilized class I-peptide complexes formed in vitro from antigenic peptides and purified class I molecules containing wild-type or Glu227-->Lys substituted alpha 3 domains. The alpha 3 domain mutant class I-peptide complexes were bound by CTL and triggered degranulation, however to much lower levels than wild-type class I-peptide complexes. In further experiments, it is directly demonstrated that the alpha 3 domain mutant class I molecules, which lack the Glu227 CD8 binding site, still serve as TCR-activated, avidity-enhanced CD8 accessory ligands. However, mutant class I peptide Ag complexes failed to effectively serve as CD8 coreceptor ligands to initiate TCR-dependent signals required to induce avidity-enhanced CD8 binding to coimmobilized non-Ag class I molecules. Thus the Glu227-->Lys mutation effectively distinguishes CD8 coreceptor and avidity-enhanced CD8 accessory functions.     

Ischemic proctosigmoiditis

Rectal ischemia is rare because of excellent collateral supply. Although rectosigmoid ischemia is usually accompanied by more proximal colonic involvement, it may occur alone. METHODS: A retrospective review of all patients diagnosed as having colonic ischemia at the Mayo Clinic from 1976 to 1991 was performed. Clinical, endoscopic, radiological, and pathological data were obtained from patient charts. Patients with involvement of the rectosigmoid colon extending to no more than 30 cm above the dentate line on endoscopy were included in the study. A single radiologist reviewed CT scans and aortograms, and a single pathologist reviewed tissue specimens. RESULTS: Ten of 328 patients with ischemic colitis had isolated ischemic proctosigmoiditis. Six patients had acute ischemia (i.e., symptom duration of less than 4 wk), and four had chronic ischemia (symptoms for 4 wk or longer). Ischemic proctosigmoiditis affects elderly patients with atherosclerosis. An identifiable precipitating factor, such as a major illness or hemodynamic disturbance, was identified in four of six patients with acute ischemic proctosigmoiditis and in one of four patients with chronic ischemic proctosigmoiditis. CT revealed rectal wall thickening and/or perirectal stranding. Angiography may demonstrate atheromatous disease of the aortoiliac vessels. Acute and "chronic" presentations had similar histopathological changes. CONCLUSIONS: Ischemic proctosigmoiditis is rare. In contrast to generalized colonic ischemia, patients with acute rectal ischemia often have clearly identifiable precipitating factors. Conservative management is appropriate for uncomplicated acute ischemic proctosigmoiditis. Patients with chronic ischemic proctosigmoiditis. Patients with chronic ischemic proctosigmoiditis may develop bowel perforation necessitating a proctectomy or colonic diversion. Recognition of this entity and differentiation from idiopathic inflammatory bowel disease is important to determine appropriate therapy.     

Effect of lung contusion on surfactant composition in multiple-trauma patients

OBJECTIVE: The aim of this study was to investigate alterations of the surfactant system in multiple-trauma patients (MTP) with lung contusion and the influence of single- or multiple-organ dysfunction syndrome (OF/MOF) on the surfactant system. SETTING: University hospital, trauma-intensive care unit. DESIGN: Prospective, nonrandomized study. METHODS: MTP with an Injury Severity Score > 19 points have been recorded prospectively since 1992. Bronchoalveolar lavages were obtained daily either until day 14 or extubation. Three groups of MTP were compared: noL: MTP, no lung contusion (n = 14); LuCo-: MTP, lung contusion, no OF/MOF (n = 17); LuCo+: MTP, lung contusion, with OF/MOF (n = 10). Also, surfactant samples of 11 healthy volunteers (Con) were investigated and compared with MTP. All data were presented as mean +/- SEM. Statistical analysis were performed using programs of SPSS 6.0.1. (univariate ANOVA, Fisher's Exact Test, p < = 0.05). RESULTS: There were no differences in sex and age. Injury Severity Score was significantly impaired in group LuCo+ (44 +/- 4), compared with groups noL (31 +/- 3) and LuCo- (34 +/- 3). Group noL showed no statistical differences for lung function, total protein, and total phospholipid content of the bronchoalveolar lavage compared with group LuCo-. Furthermore, the relative content of phosphatidylcholine and phosphatidylglycerol in total phospholipids and surfactant-associated protein A were not significantly altered compared with group LuCo-. Lung function in group LuCo+ was significantly impaired and led to hypoxemia on the day of trauma. Total protein content and total phospholipids were significantly elevated in group LuCo+ compared with groups noL and LuCo- on the first day. Also, the relative content of phosphatidylcholine was significantly increased in group LuCo+ up to day 4, compared with groups noL and LuCo-. In comparison with groups noL and LuCo-, a significant decrease of the relative content of phosphatidylglycerol was obtained in group LuCo+ up to day 7. The surfactant-associated protein A was increased in group LuCo+ during the whole observation time, compared with the other groups. CONCLUSIONS: Multiple trauma leads to alterations in the surfactant system. The composition of surfactant was not further influenced by lung contusion alone. Only MTP with OF/MOF during the intensive care unit treatment showed significant alterations in surfactant composition and a decrease in lung function.     

The effects of diet, ad libitum overfeeding, and moderate dietary restriction on the rodent bioassay: the uncontrolled variable in safety assessment

Ad libitum (AL) overfeeding is the most significant, uncontrolled variable affecting the outcome of the current rodent bioassay. There is a highly significant correlation between AL food consumption, the resultant obesity and body weight, and low 2-yr survival in rodents. AL feeding of diets with lowered protein, metabolizable energy (ME), and increased fiber does not improve survival. Only dietary restriction (DR) of all diets tested significantly improves survival and delays the onset of spontaneous degenerative disease (i.e., nephropathy and cardiomyopathy) and diet-related tumors. Moderate DR results in an incidence of spontaneous tumors similar to AL-fed rats, but the tumors are found incidentally and do not cause early mortality. There is a decreased age-adjusted incidence of pituitary and mammary gland tumors in moderate DR-fed rats, but tumor growth time is similar between AL and DR rats with only a delay in tumor onset time seen in DR-fed groups. Moderate DR does not significantly alter drug-metabolizing enzyme activities nor the toxicologic response to 5 pharmaceuticals tested at maximum tolerated doses (MTDs). However, moderate DR-fed rats did require much higher doses of 4 additional pharmaceutical compounds before classical MTDs were produced. Toxicokinetic studies of 2 of these compounds demonstrated equal or higher steady-state systemic exposures to parent drug and metabolites in moderate DR-fed rats. Markers of oxidative stress (lipid peroxidation, protein oxidation) are decreased and cytoprotective anti-oxidant markers are preserved in moderate DR-fed rats. But moderate DR does not delay reproductive senescence in female rats. Only marked DR delays reproductive senescence compared to AL and moderate DR-fed female rats. These and other data indicate that moderate DR is the most appropriate method of dietary control for the rodent bioassay when used to assess pharmaceuticals for human safety and compounds for risk assessment.