Evidence for dual modulation of pepsinogen secretion using isoproterenol, carbachol, CCK-8, forskolin, 8 bromo-cAMP, and A23187 probes

The cellular mechanisms by which pepsinogen (PNG) secretion is controlled are not understood. The aim of this study was to explore whether modulation of PNG secretion is mediated by cAMP or calcium-calmodulin (C-C). PNG secretion in isolated rabbit gastric fundic glands (IGG) was tested, using agents believed to act via cAMP or C-C. IGG were stimulated for 30 minutes with histamine (H) 10(-5) M, isoproterenol (I) 10(-5) M, carbachol (C) 10(-5) M, cholecystokinin-octapeptide (CCK-8) 10(-7) M, forskolin (F) 10(-5) M, 8 bromo-cAMP (8B) 10(-3) M, and A23187 (A) 10(-6) M. PNG levels were determined by spectrophotometric assay of hemoglobin digestion products. PNG amounts secreted were (mean per cent above basal levels of total IGG PNG units +/- SEM): H, -0.02 +/- 0.30%; I, 3.5 +/- 0.9%; C, 5.1 +/- 2.2%; CCK-8, 5.3 +/- 1.5%; F, 10.6 +/- 3.8%; 8B, 13.8 +/- 4.5%; A, 2.1 +/- 1.1%. All secretagogues except H stimulated PNG release significantly above basal levels (p less than 0.05). A primary histaminergic mechanism for pepsinogen secretion is unlikely. Since two other adenylate cyclase activators, isoproterenol and forskolin and the 3':5'-cyclic adenosine monophosphate analog 8-bromo cAMP stimulated pepsinogen secretion, cAMP-dependence is probable. Since carbachol, CCK-8, and A23187, which are believed to act via calcium-calmodulin, also stimulated pepsinogen secretion, this system, too, presumably plays a substantial role. Thus the data support a dual 3':5'-cyclic adenosine monophosphate/calcium-calmodulin modulation of pepsinogen secretion.     

Indwelling Versus Intermittent Feeding Tubes in Premature Neonates

Objective: To determine the effect of indwelling versus intermittent feeding tube placement on weight gain, apnea, and bradycardia in premature neonates.
Design: Eligible subjects were assigned randomly to either feeding tube method. Each subject was followed for 6 days.
Setting: The study was conducted in a secondary level neonatal intensive-care unit (NICU), a tertiary level NICU in a perinatal center, and a tertiary level NICU in a referral center.
Patients/Participants: Neonates who were 24–34 weeks gestational age, developmentally appropriate for gestational age, medically stable, on full enteral feedings through an orogastric or a nasogastric tube, and not fluid restricted. Ninety-three neonates were enrolled-49 in the indwelling group and 44 in the intermittent group. Nine neonates did not complete the study.
Interventions: Nasogastric indwelling feeding tubes were placed and left in site for up to 3 days. Orogastric intermittent feeding tubes were placed for each feeding and removed at completion of the feeding.
Main outcome measures: Weight gain, apnea, and bradycardia. Results: Members of both groups had similar demographic characteristics, clinical problems, and nutritional intake. No statistical differences were found between the two groups in weight gain or episodes of apnea and bradycardia.
Conclusions: There were no statistically or clinically significant differences between the two groups. The intermittent method of feeding is more expensive. Because no clinical differences were found, the type of tube placement chosen for feeding the premature infant may be based on economics.     

Suppurative corneal ulceration in Bangladesh

Suppurative keratitis is an important preventable cause of blindness, particularly in the developing world. This study analyses 142 cases of suppurative keratitis referred to Chittagong Eye Infirmary, Bangladesh. Some 53.5% of cases were bacterial and 35.9% were fungal. The five most common pathogens were: Pseudomonas sp. 24%, Streptococcus pneumoniae 17%, Aspergillus sp. 13%, Fusarium sp. 7% and Curvularia sp. 6%. Gram stain and culture results were consistent in 62.6% of cases. Previous antibiotic treatment was a significant factor for failure of culture isolation and less so for Gram stain failure. On Gram stain, 55.9% of pseudomonal cases were missed, but only 2% of fungal cases were missed. Over all, Gram stain had a sensitivity of 62% and positive predictive value of 84% for bacterial cases, and 98% and 94% for fungal cases, respectively. Fungal ulcers were typically filamentous, but an antecedent history of trauma was not common. The most frequent injury was due to rice grains, but the inoculum appeared to be introduced during eye washing with contaminated water. Pseudomonal ulcers occurred most frequently in the monsoon season, and Fusarium cases were seen only in the hot, dry season.     

The effects of preservation on microvascular vein grafts in rats

Segments 15 mm in length were excised from the femoral veins of rats and preserved by refrigeration at 4 C in lactated Ringer's solution for periods up to 21 days. The findings show that veins can be preserved for up to seven days and successfully grafted to recipients. Although there was some success in preserving vein segments for more than seven days, a high rate of thrombosis occurred after implantation in the recipients. It is generally accepted that damaged endothelium causes thrombosis. The light and electron microscopic observations in this study, however, suggest that the condition of the endothelium may not be the only important factor in the patency of small vessels. A thickened and prominent elastic lamina may also play a role in keeping the lumen open.     

Nonheme iron in sickle erythrocyte membranes: association with phospholipids and potential role in lipid peroxidation

Previous studies documented the abnormal association of heme and heme proteins with the sickle RBC membrane. We have now examined RBC ghosts and inside-out membranes (IOM) for the presence of nonheme iron as detected by its formation of a colored complex with ferrozine. Sickle ghosts have 33.8 +/- 18.2 nmol nonheme iron/mg membrane protein, and sickle IOM have 4.3 +/- 3.0 nmol/mg. In contrast, normal RBC ghosts and IOM have no detectable nonheme iron. The combination of heme and nonheme iron in sickle IOM averages nine times the amount of membrane- associated iron in normal IOM. Kinetics of the ferrozine reaction show that some of this nonheme iron on IOM reacts slowly and is probably in the form of ferritin, but most (72% +/- 18%) reacts rapidly and is in the form of some other biologic chelate. The latter iron compartment is removed by deferoxamine and by treatment of IOM with phospholipase D, which suggests that it represents an abnormal association of iron with polar head groups of aminophospholipids. The biologic feasibility of such a chelate was demonstrated by using an admixture of iron with model liposomes. Even in the presence of tenfold excess adenosine diphosphate, iron partitions readily into phosphatidylserine liposomes; there is no detectable association with phosphatidylcholine liposomes. To examine the bioavailability of membrane iron, we admixed membranes and t-butylhydroperoxide and found that sickle membranes show a tenfold greater peroxidation response than do normal membranes. This is not due simply to a deficiency of vitamin E, and this is profoundly inhibited by deferoxamine. Thus, while thiol oxidation in sickle membranes previously was shown to correlate with heme iron, the present data suggest that lipid peroxidation is related to nonheme iron. In control studies, we did not find this pathologic association of nonferritin, nonheme iron with IOM prepared from sickle trait, high-reticulocyte, postsplenectomy, or iron-overloaded individuals. These data provide additional support for the concept that iron decompartmentalization is a characteristic of sickle RBCs.     

Current clinical laboratory practice: investigation of plasma lipids--which tests and when?

Clinical interest in the lipoproteins stems mainly from the association between serum cholesterol concentrations and coronary heart disease. Investigations of lipoproteins should be performed in patients with premature coronary heart disease, with a strong family history of coronary heart disease, or with certain cutaneous stigmata of hyperlipoproteinaemia and when fasting serum samples are seen to be lipaemic. Family studies should be performed in appropriate cases to identify relatives at increased risk of developing coronary heart disease. Patients with conditions known to cause secondary hyperlipoproteinaemia should be investigated if they fall into one of these categories but only after treatment of the underlying condition. Non-specialist laboratories should be able to measure total cholesterol and triglyceride concentrations and high density lipoprotein cholesterol concentrations. Lipoprotein electrophoresis has a limited role in such laboratories and is not necessary as a routine procedure. Specialist laboratories should in addition be able to measure individual lipoproteins and identify apolipoprotein E phenotypes.