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Biomedical subjects

J R Hamilton

Publications and source records attributed to J R Hamilton.

At least 55 records · Page 3Linked to original sources
PubMed1997

High prevalence of anemia after cardiac transplantation in children.

BACKGROUND: Chronic anemia is common in adults after successful cardiac transplantation. However, the prevalence of anemia in children after cardiac transplantation is uncertain. The purpose of this study was to investigate the prevalence and causes of chronic anemia in well children after cardiac transplantation and in particular to define the role, if any, of iron deficiency, which is important and relatively common in normal children. METHODS: Twenty children (ages 7 months to 16 years) who were well 4 months to 6 years after cardiac transplantation were studied. Fourteen children (70%) were anemic and enrolled in a prospective trial of iron supplementation. RESULTS: In the majority of children, serum iron and erythropoietin levels were low, although serum ferritin and zinc protoporphyrin levels tended to be normal or high. Only one child demonstrated a definite response to iron supplementation, although the hemoglobin level remained low. CONCLUSIONS: Anemia is highly prevalent in this population, and, despite the presence of low serum iron and transferrin saturation, anemia is not usually due to iron deficiency. Although the diagnosis of iron deficiency in this group is difficult and must not be missed, inappropriate therapy should be avoided. In the majority of children, there appears to be an anemia of chronic disease which may be secondary to chronic inflammation or an effect of cyclosporine on erythropoietin production.

Adolescent↗
PubMed1997

Recurrent pneumomediastinum and pneumothorax in Langerhans cell histiocytosis.

Pneumothorax is an unusual complication of pulmonary Langerhans cell histiocytosis. We report three children who developed recurrent intrathoracic air leaks. In one case, bilateral pneumothoraces may have been precipated by intermittent positive pressure ventilation during general anaesthesia. Chemical pleurodesis was unsuccessful in preventing recurrence of pneumothoraces in two children. The use of extracorporeal membrane oxygenation as an alternative to intermittent positive pressure ventilation in children with respiratory failure from Langerhans cell histiocytosis is discussed.

Adolescent↗
PubMed1996

Activation of Na+/H+ exchange is required for regulatory volume decrease after modest "physiological" volume increases in jejunal villus epithelial cells.

Epithelial cell volume increases that occur because of the uptake of Na+-cotransported solutes or hypotonic dilution are followed by a regulatory volume decrease (RVD) due to the activation of K+ and Cl- channels. We studied the relationship of Na+/H+ exchange (NHE) to this RVD in suspended guinea pig jejunal villus cells, using electronic sizing to measure cell volume changes and fluorescent spectroscopy of cells loaded with 2', 7'-bis(carboxyethyl)-5()-carboxyfluorescein to monitor intracellular pH (pHi). When the volume increase achieved by these cells during Na+ solute absorption was duplicated by a modest 5-7% hypotonic dilution, their pHi first acidified and then alkalinized. This alkalinization was blocked by 5-(N-methyl-N-isobutyl) amiloride (MIA; 1 microM), an inhibitor of NHE. The RVD subsequent to 5-7% hypotonic dilution was prevented by Na+-free medium and by amiloride and non-amiloride derivatives. The order of potency of these inhibitors was as follows: MIA > 5-(N,N-dimethyl) amiloride > cimetidine > clonidine, in keeping with the pattern attributable to NHE-1 as the isoform of NHE responsible for increase in pHi after modest volume increases. A substantial 30% hypotonic dilution caused acidification, and RVD following this larger volume increase was not affected by MIA. To assess the effect of hypotonicity on the activity of NHE, we measured the rate of MIA-sensitive pHi recovery from an acid load (dpHi/dt) in 5 and 30% hypotonic media. pHi recovery was faster in 5% hypotonic medium compared with isotonic medium and slowest in 30% hypotonic medium, which suggested that the activity of NHE was stimulated in the slightly hypotonic medium, but inhibited in the 30% hypotonic medium. To determine the role of activated NHE in RVD after a modest volume increase, cells were hypotonically diluted 7% in MIA to prevent RVD and then alkalinized by NH4Cl or acidified by propionic acid addition. Only after alkalinization was there complete volume regulation. We conclude that in Na+-absorbing enterocytes, the NHE-1 isoform of Na+/H+ exchange is stimulated by volume increases that duplicate the "physiological" volume increase occurring when these cells absorb Na+-cotransported solutes. The subsequent alkalinization of pHi is a required determinant of the osmolyte loss that underlies this distinct volume regulatory mechanism.

Alkalies↗
PubMed1996

Treatment of Mycobacterium avium complex infection: do the results of in vitro susceptibility tests predict therapeutic outcome in humans?

The ability of various in vitro methods of antibiotic susceptibility testing to predict therapeutic outcome in patients infected with Mycobacterium avium complex (MAC) was evaluated. Pretreatment bloodstream MAC isolates from 38 patients with AIDS, previously treated in a randomized fashion with either ethambutol, rifampin, or clofazimine, were tested by three conventional methods using broth or agar, as well as by cocultivation with macrophages. The results obtained with each method were compared with the quantitatively determined bacteriologic response to the administration of the single agent in humans. None of the conventional in vitro susceptibility methods was predictive of therapeutic outcome, while the results of cocultivation with macrophages were of moderate predictive value. The positive predictive value of a response in humans based on a response in macrophages (defined by > or = to 1.0 log reduction in baseline colony counts after 5 days of treatment) was 74%. The negative predictive value was 82%.

AIDS-Related Opportunistic Infections↗
PubMed1996

Treatment of Myocardium avium complex infection: does the beige mouse model predict therapeutic outcome in humans?

To determine the predictive value of a standard murine model in the treatment of disseminated Myocardium avium complex (MAC) infection, beige mice were infected with MAC strains isolated from human immunodeficiency virus-infected patients and treated with the same antibiotic (ethambutol, clofazimine, or rifampin) that had been administered to the subject from whom that strain had been recovered. While ethambutol had the greatest bacteriologic efficacy in humans (mean decrease +/-SD, 1.0+/-0.5 log 10 cfu/mL of blood), clofazimine had the greatest bacteriostatic efficacy in mice (mean decrease +/- SD, 2.8 +/- 0.7 log(10) cfu/g of tissue). A linear correlation was not observed between bacteriostatic activity in mouse liver or spleen and the degree of bacteriologic response in humans (P > or = to .1). Odds ratios for a response in humans based on a bacteriologic response in mice were not significant for each agent (P > or = to .1, all cases).

AIDS-Related Opportunistic Infections↗
PubMed1996

D-mannitol in cerebrospinal fluid of patients with AIDS and cryptococcal meningitis.

Cryptococcal meningitis (CM) is associated with raised intracranial pressure which is linked with serious neurological sequelae. Cryptococcus neoformans produces D-mannitol in vitro and in experimental meningitis in rabbits. Mannitol present in the cerebrospinal fluid (CSF) of CM patients could exacerbate raised intracranial pressure and contribute to neurological damage. To link CSF mannitol to cryptococcal infection, levels of mannitol in the CSF of AIDS patients with CM were measured by gas-liquid chromatography. Mannitol was detected in 19 of 21 samples (range, 1.5 to 26.2 mg/liter), but there was no quantitative correlation between the mannitol concentration and the cryptococcal antigen titer.

AIDS-Related Opportunistic Infections↗
PubMed1996

Sodium-bicarbonate cotransport in guinea pig ileal crypt cells.

Prior studies show that ileal HCO3- secretion is of crypt origin, possibly involving Na+-HCO3- cotransport. To test for the latter, we isolated crypt cells from guinea pig ileum and determined effects of medium HCO3-, Na+, K+, disulfonic stilbenes, and gramicidin on intracellular pH [pHi;2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein fluorescence], cell volume (electronic sizing), and Na+ efflux from 22Na+ -preloaded cells. Ileal crypt cells alkalinized when placed in sodium gluconate-HCO3- medium containing N-5-methyl-5-isobutyl amiloride (1 microM), bumetanide (10 microM) and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (250 microM which blocks Cl-/HCO3- exchange but not Na+ dependent HCO3- uptake). Depolarization with either gramicidin (50 microM) or 50 mM K+ caused a further 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS)-inhibitable increase in pHi. Gramicidin also caused SITS-inhibitable cell swelling. Both gramicidin effects were Na+ dependent: at 0 mM Na+, gramicidin acidified and did not alter cell volume; at 25 mM, gramicidin also acidified; at 90 and 140 mM, gramicidin alkalinized and induced cell swelling. HCO3- -dependent SITS-inhibitable Na+ efflux from 22Na+ -preloaded cells was also seen. We conclude that ileal crypt cells engage in electrogenic Na+ -HCO3- symport.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1995

Inhibition of intestinal secretion by rice.

Rates of stool output are reduced when cooked rice is incorporated into oral rehydration solutions. We found that a fraction extracted from rice inhibited the response of intestinal epithelial crypt cells to adenosine 3'5'-cyclic monophosphate, a major intracellular mediator of secretion. This response to rice was seen as an inhibition of cell shrinkage and of chloride efflux in fresh suspended guinea pig crypt cells. The active fraction was of low molecular weight (< 1.5 kDa), hydrophobic, and not a peptide or glycoprotein. It may be chloride-channel blocker.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Gingival overgrowth in paediatric cardiac transplant patients: a study of 19 patients aged between 2 and 16 years.

It is well established that both cyclosporin and nifedipine are associated with gingival overgrowth. However, there is little information on the prevalence of this undesirable effect in paediatric patients. The present study investigated gingival overgrowth in 19 cardiac transplant patients aged 2 years 8 months to 16 years 3 months (1.5-8.5 years post-transplant) and related such changes to variables of daily cyclosporin dosage, trough blood cyclosporin concentration and daily nifedipine dosage. Ten patients showed clinically significant gingival overgrowth and nine relatively minor overgrowth; there was no significant difference between the two groups with respect to age, length of time post-transplant, cyclosporin dosage, whole blood concentration of cyclosporin or intake of nifedipine. The expression of gingival changes therefore did not relate to any drug variable in this group of subjects.

Adolescent↗
PubMed1994

Progressive immunodeficiency due to infection with human immunodeficiency virus does not lead to waning immunity to measles in a cohort of homosexual men.

The relationship between progressive immunodeficiency related to infection with human immunodeficiency virus (HIV) and waning immunity to measles was investigated in this retrospective cohort study. Titers of serum antibodies to measles virus were measured by enzyme immunoassay of stored sera from a cohort of homosexual men who were studied at San Francisco General Hospital. Subjects underwent a baseline and follow-up measure of measles antibodies. High levels of antibodies to measles virus were maintained in the HIV-positive and negative groups. One (2%) of the 50 HIV-negative controls was seronegative for the measles virus, and no controls evidenced seroreversal (decline in antibody to a level at which protection is not provided) during the study. Two (1.4%) of the 145 HIV-positive subjects were measles-seronegative, and two others evidenced seroreversal. Analysis with Spearman's rank correlation revealed no relationship between changes in the CD4 cell count and measles antibody level. Thus we conclude that waning measles immunity is not greatly accelerated in HIV-infected adults despite progressive HIV-related immunodeficiency.

Adult↗
PubMed1994

Isotonic volume reduction associated with cAMP stimulation of 36Cl efflux from jejunal crypt epithelial cells.

To determine the effect of 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) on the isotonic volume of jejunal crypt epithelial cells, we isolated these cells by sequential perfusion using a hyperosmolar Ca(2+)-free solution and measured cell volume electronically. 8-BrcAMP caused rapid shrinkage to a reduced but stable cell volume; this isotonic volume reduction was prevented by either a Cl(-)-channel blocker, anthracene-9-carboxylate (A-9C), or Ba2+, a K(+)-channel blocker. 8-BrcAMP substantially increased the rate of A-9C-sensitive 36Cl efflux from crypt cells; this increased rate of efflux was not influenced by Ba2+ but was abolished by alterations in membrane potential. Following 8-BrcAMP-stimulated isotonic volume reduction, addition of either Ba2+ or A-9C caused the crypt cells to reswell. In contrast, 8-BrcAMP added to enterocytes isolated from the villus compartment did not result in A-9C-sensitive volume reduction or in an increased rate of 36Cl efflux. Our data demonstrate that epithelial cells isolated from jejunal crypt compartments respond directly to cAMP with a rapid volume reduction that is paralleled by an increase in 36Cl efflux through a conductive pathway. Unlike other Cl- secretory epithelial cells, the intestinal crypt cell does not appear to regulate its volume in an isotonic medium after cAMP-induced shrinkage.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

Developmental differences of cystic fibrosis transmembrane conductance regulator functional expression in isolated rat fetal distal airway epithelial cells.

Fluid secretion from the pulmonary epithelium may play a significant role in determining intrauterine lung development. We used suspensions of distal pulmonary epithelial cells isolated from rat fetuses to assess a shift in secretory mechanisms occurring in the lung of this species during late gestation. The impact of cAMP on distal airway epithelial cells isolated from d 18 to d 21 rat fetuses was evaluated with measurements of cell volume and 36Cl efflux rates. At d 18, 8-Br-cAMP stimulated a volume reduction measured by electronic cell sizing that was prevented by the Cl- channel blocker anthracene-9-carboxylate (A-9C) and reflected in an increased rate of A-9C sensitive 36Cl efflux. Because the cystic fibrosis transmembrane conductance regulator (CFTR) is thought to be a cAMP-regulated Cl- channel, we measured the effect of prior cell incubation with oligodeoxynucleotides antisense to the transcription site of the human CFTR gene on these events. We found that in antisense oligomer-treated cells, but not in sense oligomer-treated controls, volume and 36Cl efflux responses to 8-Br-cAMP were prevented in d 18 cells. In d 21 cells, 8-Br-cAMP did not stimulate volume reduction but the calcium ionophore A23187 did elicit cell volume reduction in cells suspended in an isotonic Ca(2+)-containing medium that was prevented by A-9C. This response to the ionophore was not found in the d 18 cells, and incubation with the antisense CFTR oligomer had no effect on the ionophore-induced responses in d 21 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗