Biomedical subjects

M Shields

Publications and source records attributed to M Shields.

18 recordsLinked to original sources

PubMed1992

Efficacy of adding nebulized ipratropium bromide to nebulized albuterol therapy in acute bronchiolitis.

Nebulized ipratropium bromide is though to be synergistic with albuterol in therapy for acute childhood asthma. Because the efficacy of ipratropium in bronchiolitis is uncertain and some infants with bronchiolitis do not respond to nebulized albuterol alone, the following study was undertaken. In this double-blind, placebo-controlled trial, 69 infants between 6 weeks and 24 months of age who exhibited the first episode of acute bronchiolitis were randomly assigned to receive either nebulized albuterol (0.15 mg/kg per dose) and ipratropium bromide (250 micrograms per dose) (group A, n = 36) or nebulized albuterol and normal saline (placebo) (group B, n = 33) for two doses, 1 hour apart. The two groups were comparable at baseline. Both therapies resulted in clinically significant improvement. However, the addition of ipratropium resulted in no additional benefit with respect to decrease in the respiratory rate (mean decreases 10.6/min vs decreases 8.6/min, P = .86), accessory muscle score (range 0 through 3) (decreases 0.92 vs decreases 0.82, z = -0.44), wheeze score (range 0 through 3) (decreases 0.94 vs 0.85, z = -0.20), oxygen saturation (increases 0.25% vs increases -0.33%, P = .86), or hospitalization rate (17 vs 10). The number of "nonresponders" and "clear responders" was also very similar in both groups. No toxicity was noted. The increase in heart rate was mild and similar in both groups (increases 6.7 vs increases 11.1). The power of the study to detect a difference between the two treatment groups in the respiratory rate change > or = 8/min is greater than 90%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1991

Acetaminophen does not impair clearance of zidovudine.

OBJECTIVE: To determine whether concurrent treatment with acetaminophen and zidovudine impairs clearance of zidovudine, thereby increasing the risk for zidovudine-induced hematologic toxicity. DESIGN: Dose escalation, drug interaction study. SETTING: University clinical research center. PATIENTS: Patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex. INTERVENTIONS: Acetaminophen and 200 mg of zidovudine simultaneously every 4 hours. For 13 patients, the unit dosage of acetaminophen was 325 mg for 3 days; for 8 patients, the dosage was 650 mg for 3 days; and, for 6 patients, the dosage was 650 mg for 7 days. MEASUREMENTS: Zidovudine clearance and production of the glucuronide conjugate of zidovudine were assessed after acetaminophen treatment. MAIN RESULTS: Neither zidovudine clearance nor production of the glucuronide conjugate of zidovudine was impaired after treatment with acetaminophen. Clearance of zidovudine was actually accelerated by 5%, 11%, and 33% with the three acetaminophen regimens, respectively (P = 0.002 by analysis of variance; P = 0.04 for linear trend when changes in the area-under-the-curve for zidovudine were compared). CONCLUSION: Because serum concentrations of zidovudine decrease after the coadministration of acetaminophen, a pharmacokinetic interaction between zidovudine and acetaminophen is unlikely to increase the risk for hematologic toxicity associated with zidovudine.

AIDS-Related Complex↗

PubMed1991

Pulmonary hemorrhage and necrotizing glomerulonephritis without glomerular immune deposits: report of two cases.

Two children with a syndrome of pulmonary hemorrhage and necrotizing, nonimmune glomerulonephritis are reported. A boy and girl, both of East Indian descent, developed recurrent lung infiltrates from the age of 3 months and 2 years, respectively. Both subsequently presented with pulmonary hemorrhage, fever, arthritis, hematuria, and nephrotic range proteinuria at 1.5 and 6 years of age, respectively. Renal biopsy in each case showed acute, severe, focal and segmental, necrotizing and crescentic glomerulonephritis without immune deposits. Subsequent renal biopsies revealed severe glomerular and tubulointerstitial scarring. No vasculitis or granulomas were seen on renal, skin, or lung biopsies. Antineutrophil cytoplasmic antibodies (ANCA) were not detected in sera taken 1.5 years in the boy and 3.5 years in the girl after the onset of renal disease. The boy was treated with prednisone, azathioprine, and plasmapheresis, but developed progressive renal impairment and commenced dialysis within 4 years. Subsequent to renal transplantation, he developed an immunoblastic lymphoma and died. The girl was treated initially with prednisone and later with cyclophosphamide. After 4 years, she had a normal glomerular filtration rate (GFR). While necrotizing nonimmune glomerulonephritis associated with pulmonary hemorrhage is rare, and cases are characteristically difficult to classify because of many overlapping features, it is possible that these children had a unique illness.

Child↗

PubMed1990

PCB reduction and clinical improvement by detoxification: an unexploited approach?

1. A detoxification trial was administered to a female worker from a capacitor factory who had been exposed to polychlorinated biphenyls (PCBs) and other lipophilic industrial chemicals. 2. The patient presented with severe abdominal complaints, chloracne, liver abnormalities, and a spontaneous nipple discharge of approximately 50 ml d-1. 3. PCB levels were high in adipose tissue (102 mg kg-1), serum, (512 micrograms l-1), skin lipids (66.3 mg kg-1), and in the nipple discharge (712 micrograms l-1). 4. The patient's history, the medical evaluation and prior unsuccessful symptomatic treatments were indicative of consequences elicited by occupational exposure to chemicals. 5. Detoxification treatment reduced the PCB levels in adipose tissue to 37.4 mg kg-1 and in serum to 261 micrograms l-1, a 63% and 49% reduction, respectively. 6. The nipple discharge ceased and the symptoms improved. 7. Excretion of intact PCBs in sebum was appreciable before treatment and was enhanced by up to five-fold during detoxification. 8. This therapeutic approach appears promising for cases involving occupational exposure to lipophilic chemicals.

Acne Vulgaris↗

PubMed1988

Production of a positive direct antiglobulin test due to suramin.

Drugs and chemicals containing multiple reactive carbonyl groups have been postulated to produce nonimmunologic positive direct antiglobulin tests (DATs) both in vitro and in vivo. Suramin sodium, a reverse transcriptase inhibitor that was under investigation as a potential treatment for human immunodeficiency virus infection, has six reactive carbonyl groups. Because of suramin's chemical structure, it was hypothesized that the drug might cause a positive DAT in vitro and possibly in vivo. Suramin was found to produce a positive DAT in vitro at concentrations of 2100 mg/L or greater but did not cause a positive DAT in five patients with acquired immunodeficiency syndrome who were treated with suramin, probably because the serum levels of suramin were too low in these patients (peak therapeutic blood levels ranged from 171 to 443 mg/L).

Acquired Immunodeficiency Syndrome↗

PubMed1987

Effects of intracellular Ca2+ and proteolytic digestion of the membrane skeleton on the mechanical properties of the red blood cell membrane.

Intracellular Ca2+ at concentrations ranging from 0 to 10 mumol/l increases the shear modulus of surface elasticity (mu) and the surface viscosity (eta) of human red blood cells by 20% and 70%, respectively. K+ selective channels in the red cell membrane become activated by Ca2+. The activation still occurs to the same extent when the membrane skeleton is degraded by incorporation of trypsin into resealed red cell ghosts, suggesting that the channel activation is not controlled by the proteins of the membrane skeleton and is independent of mu and eta. Incorporation of trypsin at concentrations ranging from 0 to 100 ng/ml into red cell ghosts leads to a graded digestion of spectrin, a cleavage of the band 3 protein and a release of the binding proteins ankyrin and band 4.1. These alterations are accompanied by an increase of the lateral mobility of the band 3 protein which, at 40 ng/ml trypsin, reaches a plateau value where the rate of lateral diffusion is enhanced by about two orders of magnitude above the rate measured in controls without trypsin. Proteolytic digestion by 10-20 ng/ml trypsin leads to a degradation of more than 40% of the spectrin and increases the rate of lateral diffusion to about 20-70% of the value observed at the plateau. Nevertheless, mu and eta remain virtually unaltered. However, the stability of the membrane is decreased to the point where a slight mechanical extension, or the shear produced by centrifugation results in disintegration and vesiculation, precluding measurements of eta and mu in ghosts treated with higher concentrations of trypsin. These findings indicate that alterations of the structural integrity of the membrane skeleton exert drastically different effects on mu and eta on the one hand and on the stability of the membrane on the other.

Calcium↗

PubMed1985

Lead-induced activation and inhibition of potassium-selective channels in the human red blood cell.

The selective increase of net K+ permeability in human red cells brought about by either Ca2+ or lead was studied using a light scattering technique to measure net K+ fluxes in cell suspensions and the patch-clamp technique to study K+ transport in individual K+-selective channels of the red cell membrane. Using ultrapure solutions it was demonstrated that the effect of lead is neither the indirect consequence of a lead-induced increase of the accessibility of the receptor sites of the K+-selective channels to traces of Ca2+ that are present as contamination in analytical grade reagents nor to the release of Ca2+ from intracellular Ca2+ stores. It is further shown that in cell-free membrane patches low concentrations of lead (10 microM) in Suprapur solutions evoke the same single-channel events as added Ca2+ and that this activity can be inhibited by high concentrations of lead (100 microM), similar to the net KCl efflux measured by means of the light scattering technique. It is concluded, therefore, that both Ca2+ and lead independently activate the same K+-selective channels in the red cell membrane.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1985

Open letter to women who have ever used an IUD.

Explore the source record for details and available documents.

Female↗

PubMed1985

Subarachnoid space: middle ear pathways and recurrent meningitis.

Congenital bony abnormalities of the inner ear may result in a communication between the middle ear and the subarachnoid space. Patients with this anomaly often present with recurrent meningitis associated with acute otitis media or with middle ear fluid. This article presents three cases of recurrent meningitis with open middle ear--subarachnoid space connections. The first two cases involve a cerebrospinal fluid leak into the middle ear via the oval window, both patients having a Mondini-type of inner ear deformity. The pathway in the third case opened into the middle ear along the horizontal portion of the facial nerve. Computed tomography (CT) scanning with metrizamide and differential density calculations helped to identify the abnormal pathway and to confirm that the leak has been closed postoperatively. Use of the CT scanner in these cases can be helpful in planning the surgical closure and in postoperative follow-up.

Adolescent↗

PubMed1983

The association between prolyl hydroxylase metabolism and cell growth in cultured L-929 fibroblasts.

Prolyl 4-hydroxylase (EC 1.14.11.2) is a key enzyme in collagen biosynthesis, its active form is a tetramer (alpha 2 beta 2). In L-929 fibroblasts in the log phase of culture there is a low level of active enzyme. When the cell culture reaches confluency, prolyl hydroxylase activity in cells increases by a process that requires de novo RNA and protein synthesis. The same result may be achieved by crowding the cells (replating log phase cells at the density of stationary phase cells). In the work reported here we further examined induction of the enzyme. RNA synthesis necessary for enzyme induction is complete 6 h after "crowding" while protein synthesis requires 12 h. Thymidine (0.2-0.5 mM) added to log phase cells will also cause enzyme induction to the level found in "crowded" or resting cells. We also looked at the decay of the enzyme activity after subculture. This occurs rapidly (enzyme half-life is 1-2 h) and is concurrent with the re-entry of resting cells into cell cycle; however, thymidine added at the time of subculture to block DNA synthesis does not prevent the loss of prolyl hydroxylase activity. These results suggest that when cells are not engaged in propagation, they begin to synthesize luxury proteins such as prolyl hydroxylase. However, the loss of prolyl hydroxylase during subculture is probably not a direct consequence of DNA synthesis.

Animals↗

PubMed1974