Aerosol therapy in the newborn.
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Aerosols↗
Biomedical subjects
M Silverman
Publications and source records attributed to M Silverman.
Inhibition kinetics of cationic drugs on N'-methylnicotinamide uptake by brush border membrane vesicles from the dog kidney cortex.
The effect of cationic drugs on the uptake of the prototypical organic cation N'-methylnicotinamide has been evaluated. Using purified brush border membrane vesicles prepared from dog kidney cortex and applying a rapid Millipore filtration technique, cationic drugs apparent inhibitory constants (Ki) were calculated from kinetic analysis of N'-methylnicotinamide uptake corrected for noncarrier-mediated transport (10 s uptake; outwardly directed H+ gradient; pH 7.4, 25 degrees C). All of the cationic drugs tested exhibited competitive inhibition of N'-methylnicotinamide uptake suggesting that they all share the organic base transport system at the renal proximal tubule. The Ki values were as follows, in order of decreasing apparent affinity: quinidine (0.7 microM), trimehoprim (1.3 microM), cimetidine (2.0 microM), famotidine (3.0 microM), quinine (7.0 microM), amiloride (5.8 microM), procainamide (21 microM), and nizatidine (30 microM). The different relative affinities of the drugs for the organic base transport system may explain the mutual competition for renal tubular secretion observed when cationic drugs are administered concurrently in vivo, e.g., trimethoprim--procainamide and cimetidine--procainamide. The approach outlined in the present study should prove useful to predict complex drug interactions in clinical pharmacology.
Animals↗
The drug swindlers.
In a number of important developing nations--among them Indonesia, India, and Brazil--clinical pharmacologists and other drug experts are revealing mounting concern over the marketing of fraudulent drug products. These are shaped, colored, flavored, marked, and packaged to mimic the real product. They may contain the actual antibiotic or other drug indicated on the label, but so "cut" that the product provides only a small fraction of the labeled amount, or they may contain only useless flour or starch. At best, they are worthless. At the worst, they can kill. In most instances, it is believed that these "drugs" are produced and marketed by local or domestic fly-by-night groups and not by multinational pharmaceutical firms. Blame for these practices is placed on inadequate or unenforced laws, only trivial punishments, bribery and corruption, and the fact that generally "nobody inspects the inspectors."
Brazil↗
Diabetic glomerulopathy following unilateral nephrectomy in the dog.
To elucidate the important features of early renal disease in the diabetic dog, renal capillary permselectivity and fractional mesangial expansion with and without unilateral nephrectomy (NX) were examined. Pancreatectomized mongrel dogs (N = 9) received 10-20 U Regular and NPH insulin daily. Weekly blood glucose monitoring, 300 +/- 75 mg/dl (means +/- SD). Three dogs without NX had serial open needle biopsies 6-23 months post-pancreatectomy, revealing significant glomerular basement membrane widening and mesangial expansion. Without NX, inulin clearance increased from 2.55 +/- 0.89 (pre-diabetes) to 4.30 +/- 0.70 ml/min/kg body weight (N = 4, means +/- SD, p less than 0.05), whereas albuminuria, measured by radioimmunoassay, remained unchanged 2.57 +/- 1.03 (pre-diabetes) to 2.83 +/- 1.63 micrograms/min/kg body weight up to 23 months post-pancreatectomy. To determine whether altered renal capillary permselectivity occurred despite normal albuminuria, glomerular charge and size selectivity was analysed with serial fractional anionic dextran (20-44 A Stokes Einstein Radius) clearances. Furthermore, peritubular capillary permselectivity was probed with anionic and neutral 3H-dextran (26 A) using the multiple indicator dilution method. Fractional anionic dextran clearances remained unchanged up to 23 months, as did peritubular capillary permselectivity. Five diabetic dogs were compared to non-diabetic dogs with (N = 4) and without (N = 10) NX. To identify whether angiotensin II converting enzyme inhibition modified glomerular function or morphology, 3 diabetic + NX dogs received Captopril (5 mg/kg/day). At one year, diabetes + NX had an additive effect on renal hypertrophy, although fractional mesangial expansion was not enhanced by NX. Albuminuria was unaffected by NX or Captopril.(ABSTRACT TRUNCATED AT 250 WORDS)
Albuminuria↗
Output characteristics of DeVilbiss No. 40 hand-held jet nebulizers.
DeVilbiss No. 40 hand-held nebulizers are widely used for quantifying airway responsiveness in large populations using pharmacological agents. We examined the aerosol characteristics of five nebulizers. Within each device, the aerosol output and droplet size were reasonably stable over a wide range of bulb pressures, although there were considerable differences in output characteristics between nebulizers. The droplet size was very large compared to conventional aerosol delivery systems, with a mass median diameter greater than 10 microns for three of the five devices. Between 28-50% of the output was in particles sufficiently small for airway deposition (less than 6.2 microns). A more vigorous compression of the bulb caused a small increase output and a reduction in droplet size, resulting in a much bigger variation in the output of the respirable aerosol (less than 6.2 microns) with changes in bulb pressure. The loss due to evaporation was about 3.5%, causing a similar rise in the osmolality of the nebulizer solution. In view of the variable nebulizer output and the marked between-operator variation in bulb pressure, the characteristics of individual DeVilbiss No. 40 nebulizers should be evaluated by individual operators before use in clinical practice or research.
Aerosols↗
Marketing as a public service.
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Audiology↗
A rat hybridoma model of Heymann nephritis: production of a monoclonal anti GP330 from a nephritic rat.
Autologous (Heymann) nephritis was induced by immunizing Sprague-Dawley rats with a crude membrane extract (Fx1A) prepared from renal cortical tubules. Urine protein excretion was monitored to determine the onset of nephritis and then the spleens of nephritic rats were fused with a non-secretor rat myeloma cell line. Supernatants from hybridoma cultures were first screened for production of anti-brush border membrane (BBM) antibody by immunodot blotting of highly purified rat BBM on nitrocellulose. Positive hybrids were then tested by indirect immunofluorescence for the presence of IgG, which binds to the brush border of rat renal proximal tubules. Those hybrids which were positive by both screening assays were subcloned twice. Two monoclonal antibodies (C5, D11) were studied in some detail. Both C5 and D11 immunoprecipitated a single polypeptide from BBM, labelled with 125I by the lactoperoxidase method. Radioautography of gradient 4-11% slab sodium dodecyl sulphate polyacrylamide gels revealed that the polypeptide against which C5 and D11 were directed co-migrated with the polypeptide immunoprecipitated by (i) IgG eluted from the renal cortex of nephritic rats, and by (ii) a mouse anti-rat monoclonal against gp 330 [a BBM constituent with proven pathogenicity [9]]. Supernatants which tested positive by immunodot blotting but negative by indirect immunofluorescence showed no detectable immunoprecipitate after reaction with BBM. Immunocytochemical staining by immunoperoxidase and immunogold methods localized C5 and D11 to the BBM of the renal proximal tubule and to the urine face of the glomerular epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Isolation of a gene regulated by hydrostatic pressure in a deep-sea bacterium.
Barophilic bacteria inhabit the deep oceans, and the specific functional modifications and regulatory mechanisms which govern adaptation to hydrostatic pressure are beginning to be understood. For example, the rate of production of several proteins by some hydrothermal vent archaebacteria and the degree of saturation of membrane lipids in other deep-sea bacteria have been found to change as a result of cultivation at high pressure. We report here the cloning of gene, ompH, which encodes a major pressure-inducible protein of strain SS9, a gram-negative eubacterium isolated from a depth of 2.5 kilometres in the Sulu Sea. Messenger RNA encoded by ompH is expressed when cells are grown at 280 atm but not at 1 atm, indicating that transcription of the ompH gene is controlled by hydrostatic pressure. The function of the OmpH protein in adaptation to high pressure and the use of the ompH gene in studying how bacteria sense and respond to pressure is discussed.
Amino Acid Sequence↗
Molecular biology of the Na+-D-glucose cotransporter.
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Animals↗
Clinical significance of airway responsiveness in children of low birthweight.
We report a prospective study of airway responsiveness in a cohort of 121 children of low birthweight (under 2,000 g) at 7 years and a random sample of 100 local schoolchildren of the same age. A positive airway response was defined as a 20% fall in peak expiratory flow rate in response to a cumulative histamine dose of 3 mumol or less. We found a moderate increase in airway responsiveness to inhaled histamine in the cohort (44%) compared with the reference group (22%). There was no significant association between airway responsiveness and any perinatal variables including the level of respiratory support. The findings suggested that neonatal respiratory illness or its treatment did not play a major role in determining the long-term airway responsiveness in these children. Amongst all factors examined, reduced airway function at the age of 7 was most strongly associated with airway responsiveness, independent of perinatal and familial factors. Airway responsiveness was associated with significantly more chest symptoms. We suggest that increased airway responsiveness to inhaled histamine in low birthweight children is a consequence rather than the cause of reduced airway function and argue against the presence of any other form of airway dysfunction as a cause of airway responsiveness.
Administration, Inhalation↗
Dexamethasone in neonatal chronic lung disease: pulmonary effects and intracranial complications.
Eighteen infants were entered into a randomized, placebo-controlled trial of dexamethasone therapy for chronic lung disease. Initial ventilation requirements were similar in the two groups, although all infants were in headbox oxygen on entry to the trial. The dexamethasone-treated infants showed a significantly more rapid improvement during the 1st week of treatment, although the overall duration of oxygen therapy was similar in both groups. Cranial ultrasound examination revealed new periventricular abnormalities in three out of the five dexamethasone-treated infants who had previously normal scans, compared with none of four similar placebo-treated infants. A large trial, focussing on potential complications, is now needed.
Administration, Oral↗
Effects of the cholecystokinin receptor antagonist L-364,718 on experimental pancreatitis in mice.
The effects of the cholecystokinin receptor antagonist L-364,718 was studied in a model of mild pancreatitis induced in mice by repeated injections of the secretagogue caerulein and in a lethal form of pancreatitis induced by feeding mice an ethionine-supplemented choline-deficient diet. L-364,718 prevented the caerulein-induced rise in serum amylase and pancreatic weight in a dose-dependent manner, the most effective dose being 0.1 mg/kg body wt. L-364,718 also prevented the caerulein-induced pancreatic inflammation as seen by light microscopy. L-364,718 offered no protective effects as determined by changes in serum amylase, pancreatic weight, histology, or mortality in the ethionine-supplemented choline-deficient diet model.
Amylases↗
Tridimensional ultrastructure of glomerular capillary endothelium revealed by high-resolution scanning electron microscopy.
Recent advances in specimen preparation techniques and scanning electron microscope (SEM) design have permitted ultrastructural examination of the glomerular capillary wall in three dimensions using high-resolution scanning electron microscopy (HRSEM). Specimens in which the cytosol and cytoskeleton have been extracted, but cell membranes nuclear structures and organelles left in place, were studied using a Hitachi SEM with a resolution of approximately 3 nm. Each HRSEM micrograph displayed a depth of field and information content equivalent to 15-30 consecutive, ultrathin, transmission electron microscope (TEM) sections viewed simultaneously in perfect serial alignment. The results have confirmed previous ultrastructural observations obtained by use of TEM and, in addition, have revealed new ultrastructural features of the normal rat glomerulus. A morphometric analysis of glomerular endothelium carried out using the HRSEM micrographs revealed that the endothelial cell processes, which lie between the fenestrae, are nearly circular in cross section and that they, as well as the fenestrae, have a diameter of approximately 60 nm. The potential functional role of the fenestrae in controlling access to the underlying basement membrane requires further study.
Animals↗
Bacterial infections in the acquired immune deficiency syndrome. Clinicopathologic correlations in a series of autopsy cases.
In a group of 46 adult patients with acquired immunodeficiency syndrome (AIDS) who came to autopsy in 1983-1987, the authors found that 38 (83%) had bacterial (nonmycobacterial) infections some time during the course of their illness, compared with 34 (74%) who had parasitic infections, 31 (67%) who had viral infections, 28 (61%) who had fungal infections, and 12 (26%) who had mycobacterial infections. Twenty-five of these patients (54%) had Staphylococcus aureus infections, compared with 7 (15%) who had Pseudomonas aeruginosa infections and 6 (13%) who had enterococcal infections. Overall, undiagnosed infections or malignancies were found in 48%, 22 of the 46 autopsies, including 12 cases of undiagnosed bacterial infections, 8 of these due to S. aureus. These results suggest that bacterial infections in general, and S. aureus infections in particular, are important causes of morbidity and mortality in patients with AIDS.
Acquired Immunodeficiency Syndrome↗
Modifications in proximal tubular function induced by nitrendipine in a rat model of acute ischemic renal failure.
Calcium channel blockers have been reported to preserve renal function when given prophylactically in animal models of acute renal failure (ARF), but the mechanism by which this effect occurs is unknown. We report that nitrendipine (NTR) ameliorates the decline in endogenous creatinine clearance when administered before to clamp-induced ischemia in rats (NTR + clamp, 0.21 +/- 0.06 ml/min; clamp alone, 0.13 +/- 0.04 ml/min, p less than 0.05). To determine whether this protective effect involves the proximal tubule, we compared the uptake of phosphate by brush border membrane (BBM) vesicles in NTR-pretreated ARF rats and in ARF rats pretreated with vehicle alone. A comparison of vehicle-pretreated/sham-operated and vehicle-pretreated/ARF rats served as a control. The initial uphill phase of Na+ gradient-dependent phosphate transport was significantly greater in NTR/ARF rats as compared with vehicle/ARF rats. Pretreatment with NTR did not affect BBM transport of D-glucose or proline. We conclude that NTR has a modest protective effect on overall renal function, and that preservation of proximal tubular function is probably part of this effect.
Acute Kidney Injury↗
Airway responsiveness in infancy.
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Airway Obstruction↗
Iron regulation of swarmer cell differentiation of Vibrio parahaemolyticus.
Vibrio parahaemolyticus has two distinct cell types, the swimmer cell and the swarmer cell, adapted for locomotion in different circumstances. The swimmer cell, produced when the bacterium is grown in liquid media, is a short rod with a single sheathed polar flagellum. The swarmer cell, produced when V. parahaemolyticus is grown on solidified media, is greatly elongated and synthesizes, in addition to the polar flagellum, numerous unsheathed lateral flagella which are responsible for translocation over surfaces. We are interested in understanding how this bacterium differentiates in response to contact with surfaces and have determined in earlier work that the polar flagellum acts as a tactile sensor which controls transcription of genes (laf) encoding the swarmer cell phenotype. Surface recognition involves sensing of forces that obstruct movement of the polar flagellum. In this report we show that a second signal, iron limitation, is also required for swarmer cell differentiation. Production of lateral flagella occurred only when polar flagellar function was perturbed and iron-limiting growth conditions were imposed. The same conditions were required to induce light production in strains of V. parahaemolyticus in which a laf gene was transcriptionally fused to the lux operon encoding the enzymes for bioluminescence. The lafA gene encoding the lateral flagellin subunit was cloned and used in Northern (RNA) blot measurements. Examination of mRNA levels revealed that transcription of lafA is dependent on growth in iron-depleted media. The control of differentiation by multiple environmental stimuli is discussed.
Cell Movement↗
Nucleotide sequence of IS492, a novel insertion sequence causing variation in extracellular polysaccharide production in the marine bacterium Pseudomonas atlantica.
The complete nucleotide sequence of insertion element IS492, which causes reversible inactivation of extracellular polysaccharide production in the marine bacterium Pseudomonas atlantica, is presented. Insertion of IS492 results in the EPS- phenotype, and excision results in restoration of EPS+. DNA sequencing of the site of insertion in the eps locus showed that insertion of IS492 generates a 5-base-pair repeat and that its excision is precise. IS492 is 1,202 nucleotides in length and contains one large open reading frame encoding a protein of 318 amino acids, a candidate for transposition function. No similarity between IS492 and other transposable elements has been found. Unlike the situation with other insertion sequences, no direct or inverted repeats exist at the termini of IS492.
Amino Acid Sequence↗