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Biomedical subjects

P Bolme

Publications and source records attributed to P Bolme.

At least 37 records · Page 2Linked to original sources

Cataract development and outcome of surgery in bone marrow transplanted children.

Cataract development in bone marrow transplanted (BMT) patients was studied prospectively. There were 61 children, transplanted before the age of 18 years, who survived more than 1 year after transplantation. Patients transplanted for leukaemia (n = 43) were conditioned before BMT with cyclophosphamide (Cy) and total body irradiation (TBI). Patients with severe aplastic anaemia (SAA) (n = 9) only received Cy. None of the patients with SAA developed cataracts. All children with leukaemia, who were followed for at least 3 years (n = 37), developed lens posterior subcapsular cataracts (PSC). Cataract extraction was performed in 28 eyes, on average 5.1 years (range 3-9 years) after BMT. Postoperative corrected visual acuity was similar to that before BMT. The majority of cases needed laser capsulotomy within 2 years after cataract extraction. TBI seems to be the main cause for the high incidence of cataract after BMT. A relationship to steroid administration could not be proved, but a contributory effect is not excluded.

Adolescent↗

Expression of beta 1- and beta 2-receptor genes and correlation to lipolysis in human adipose tissue during childhood.

beta 1- and beta 2-adrenoceptor (bar1 and bar2) mRNA levels were measured in adipose tissue obtained from children (between 1 month and 10 yr of age) and adults during inguinal hernia operations. Bar1 mRNA levels were constant in all age groups studied. In infants and children less than 7 yr old, bar2 levels were twice as high (P < 0.01) as those in adults, and in infants 1-4 months old, bar2 mRNA levels were higher than bar1 levels (P < 0.01). The bar2/bar1 ratio gradually decreased, and in adults, there was 2.3-fold higher bar1 mRNA expression (P < 0.01). In infants 1-5 months old, the lipolytic sensitivity to noradrenaline was 5 times lower (P < 0.05) than that in adults, whereas the sensitivity to adrenaline and isoprenaline was unchanged. The maximal lipolytic response to adrenaline was higher than that to noradrenaline in infants (P < 0.01), whereas the opposite was found in adults (P < 0.01). The lipolytic sensitivity to the bar1-selective agonist dobutamine was not influenced by age, whereas the sensitivity to the bar2-selective agonist terbutaline was 10,000 times higher in infants than in adults. In conclusion, these data indicate subtype-specific developmental changes in bar expression, with higher bar2 mRNA levels accompanied by increased bar2-induced lipolysis during infancy.

Adipose Tissue↗

Disposition of salicylic acid in malnourished Ethiopian children after single oral dose.

The disposition of salicylic acid and salicyluric acid was studied in 57 Ethiopian children of varying nutritional status after oral administration of sodium salicylate in single doses of either 12.5 or 25 mg/kg. There was no apparent influence of nutritional status on oral salicylate disposition when related to total plasma concentrations. Unbound concentrations were predicted from total plasma concentrations on the basis of a single time point determination of protein binding in each individual, according to a Scatchard model. Areas under the unbound plasma concentration-time curve were larger and the fractional excretion of salicyluric acid was lower in children with kwashiorkor compared with control individuals. This was interpreted as lower hepatocellular metabolic activity in patients with kwashiorkor. Children with marasmus retained an unimpaired capacity for salicylate metabolism. The influence of saturable distribution and elimination are discussed.

Administration, Oral↗

Asphyctic lesion: proliferation of tyrosine hydroxylase-immunoreactive nerve cell bodies in the rat substantia nigra and functional changes in dopamine neurotransmission.

Asphyxia was induced in male rat pups by performing a delayed cesarean section on pregnant Sprague-Dawley rats. Oxygen saturation and heart rate were recorded during induction of asphyxia. Animals were sacrificed at 3 weeks of age. Brain sections were stained for tyrosine-hydroxylase (TH), dopamine-and-cyclic-AMP-regulated-phosphoprotein-32 (DARPP-32) immunoreactivity (IR) and thionein. Increasing time of asphyxia caused a reduction in the number of nerve cell bodies in the CA1 and CA3 regions of the hippocampus reflecting neuronal death. Furthermore, asphyxia resulted in an increased number of TH-IR nerve cell bodies indicative of a proliferation of dopaminergic neurons in the zona compacta of the substantia nigra. Finally, a significant decrease in rearing was observed in asphyctic animals during the habituation phase, as well as following apomorphine-induced (1 mg/kg s.c.) postsynaptic dopamine receptor stimulation. On the other hand, the apomorphine-induced increase in locomotion was enhanced in asphyctic animals. The implications of these findings for hyperkinesia and attention deficits in disorders resulting from asphyxia are discussed.

Animals↗

Craniofacial growth in bone marrow transplant recipients treated with growth hormone after total body irradiation.

The effect of growth hormone (GH) treatment on craniofacial development was studied in five children exhibiting growth retardation following bone marrow transplantation. Linear and angular measurements were made on lateral radiographic cephalograms taken prior to the start of GH treatment and after an average treatment time of 1.2 yr. The results showed that the mean growth increments of mandibular length in the GH treated children, exceeded the corresponding values of the control group by 150% during the period of investigation. It is suggested that this dimensional increase in the patients was due to GH stimulation on the chondral growth process in the mandibular condyles.

Adolescent↗

Retrospective study of children with hypophosphatasia with reference to dental changes.

In the present retrospective study different dental and medical parameters have been analyzed in 17 Swedish children with established hypophosphatasia (HP). It was demonstrated that the basis for the establishment of the diagnosis varied among different dentists and physicians, and that the diagnostic parameters studied among the children varied. The most reliable parameters for HP included raised levels of phosphoethanolamine in urine, and clinical and radiologic findings associated with the legs. These findings were found among the children more often than lowered values of alkaline phosphatase in serum. Histologic analysis of an extracted tooth made a valuable diagnostic complement. It is concluded that a better diagnostic uniformity is recommended. In a well functioning collaboration with well defined tasks, both dentists and physicians can contribute to a reliable diagnosis.

Adolescent↗

The development of cataract in children as a late side-effect of bone marrow transplantation.

Children with hematological malignancies (n = 33), severe aplastic anemia (SAA, n = 7) and other non-malignant diseases (n = 4) were followed for cataract development after bone marrow transplantation (BMT). The children with hematological malignancies were subjected to total body irradiation (TBI), 10 Gy, in one session with no shielding of the eyes as part of their conditioning regimen before BMT. The children with SAA or other non-malignant diseases received either no irradiation before BMT or a reduced dose, 8 Gy, with shielding of their eyes. After 3 years all patients who had undergone BMT for hematological malignancies had developed lens opacification. No patients in the other groups, without leukemia, showed any sign of cataract development. There was no relationship between steroid treatment for graft-versus-host disease and cataract development. No relation to age of onset of treatment or to the sex of the patient and cataract formation was seen. It seems evident from the present study that TBI given in one session was the main cause of cataract development after BMT.

Adolescent↗

Efficacy and safety of vaccination of marrow transplant recipients with a live attenuated measles, mumps, and rubella vaccine.

Long-term immunity to measles, mumps, and rubella viruses was studied in 57 patients after allogeneic bone marrow transplantation. Among patients who were seropositive at the time of transplant, 51% had retained antibodies to measles, 42% had retained antibodies to mumps, and 76% had retained antibodies to rubella 2 y later. There was no difference in the ability to retain antibodies to these viruses between patients with and those without chronic graft-versus-host disease (GVHD). Twenty seronegative patients without active chronic GVHD or ongoing immunosuppressive treatment were vaccinated with a live attenuated trivalent vaccine against measles, mumps, and rubella. No early or late side effects were detected after the vaccinations. The percentages of patients who seroconverted after vaccination were 77%, 64%, and 75% for measles, mumps, and rubella, respectively. Vaccination of transplant recipients with a live attenuated vaccine against measles, mumps, and rubella is safe and usually effective 2 y after transplant if the patients do not have active chronic GVHD or ongoing immunosuppressive treatment at the time of vaccination.

Adolescent↗

Facial growth and morphology in long-term survivors after bone marrow transplantation.

A roentgen cephalometric investigation was used to study facial growth and morphology in 17 children who had undergone bone marrow transplantation (BMT) because of acute leukaemia and aplastic anaemia. The ages at BMT varied from 1.0 to 12.9 years. Preoperative treatment included high doses of cyclophosphamide and in children with acute leukaemia also 10 Gy total body irradiation (TBI). The median observation period following BMT was 3.9 years. The control group comprised 85 age and sex matched healthy children. In comparison to the controls, all linear measurements studied were found to be significantly diminished in children conditioned with TBI. For variables describing vertical dimensions, the degree of reduction appeared to be associated with the patients' ages at the time of irradiation. It was concluded that the disturbance in dental development, which is also a consequence of TBI, could be partly responsible for this association. Children who were not conditioned with TBI exhibited no significant differences when compared to controls in respect of the variables studied.

Bone Marrow Transplantation↗

Oral mucous membrane lesions in children treated with bone marrow transplantation.

Oral mucous membrane lesions were studied in 54 children below 12 yr of age treated with allogeneic bone marrow transplantation mainly because of hematological malignancies. Sixty-two percent of the children exhibited a wide range of oral side effects during therapy. Lesions observed during the first 2 wk prior to engraftment of the donor marrow were related to the chemo- and radiotherapy given. Oral ulcerations were seen in 34% of the children. Children given methotrexate as graft-versus-host disease (GVHD) prophylaxis exhibited oral ulcerations significantly (P less than 0.05) more often than those given cyclosporin. Oral lesions related to acute GVHD were only observed in two patients. Reactivating herpes simplex virus infection was seen in 35% of the children who were seropositive prior to BMT. An extensive oral candidiasis was observed in 15% of the patients. All six children with a chronic GVHD exhibited changes in the oral mucosa 2-4 yr after transplantation such as erythma of the mucous membranes, tongue atrophy and also lichenoid changes in the buccal mucosa.

Antineoplastic Agents↗

Protein binding of salicylic and salicyluric acid in serum from malnourished children: the influence of albumin, competitive binding and non-esterified fatty acids.

The serum protein binding of salicylic and salicyluric acid has been determined by ultrafiltration in 60 children after administration of oral salicylate. The children were classified according to nutritional status: well-nourished (n = 12), underweight (n = 12), marasmic (n = 17) marasmic-kwashiorkor (n = 7) and kwashiorkor (n = 12). Salicylic acid free fractions were 0.106 +/- 0.026, 0.114 +/- 0.069, 0.141 +/- 0.037, 0.285 +/- 0.279 and 0.438 +/- 0.190 in the five groups, respectively. Salicyluric acid free fractions were 0.184 +/- 0.057, 0.280 +/- 0.282, 0.236 +/- 0.114, 0.484 +/- 0.497 and 0.646 +/- 0.261, respectively. The degree of binding was dependent on serum albumin levels, ligand concentrations and non-esterified fatty acids (NEFA). The NEFA/albumin ratio ranged from 0.05 to 6.6. The fitting of a one-site Scatchard binding model to the collective data was improved when a decrease was allowed for in the number of binding sites in proportion to NEFA concentrations. Salicyluric acid binding could be fitted only when inhibition of the parent compound was included. Binding was not affected by age or sex. The major determinants of salicylate binding in sera from malnourished children have thus been identified.

Binding, Competitive↗

Inhibition of lipolysis by agents acting via adenylate cyclase in fat cells from infants and adults.

The in vitro lipolytic effect of catecholamines is poor during infancy because of enhanced alpha 2-adrenoceptor activity. The mechanisms behind this were investigated in isolated fat cells obtained from 1- to 4-mo-old infants and from adults. The cells were incubated with agents that inhibit lipolysis through distinct receptors coupled to adenylate cyclase via the inhibitory GTP binding coupling protein, Gi. The sensitivity to the alpha 2-adrenoceptor agonist clonidine was 14 times higher in the infant group as compared to the adults, whereas that to an adenosine analogue was 14 times lower. The sensitivities to prostaglandin E2 and nicotinic acid were similar in both age groups. Preincubation of the adipocytes with pertussis toxin abolished the antilipolytic effects of all agents. The density of alpha 2-adrenoceptor binding sites determined with [3H]yohimbine was increased by about 25% in the infants. In conclusion, the antilipolytic sensitivity of adenosine and alpha 2-adrenoceptors develops separately and may play different roles in the regulation of lipolysis in man. Furthermore, the enhanced alpha 2-adrenoceptor sensitivity during infancy seems at least in part to be due to an increase in the number of receptors.

Adenylate Cyclase Toxin↗

Allogeneic bone marrow transplantation versus chemotherapy in children with acute leukemia in Sweden.

All children in Sweden who underwent bone marrow transplantation (BMT) with an HLA-identical sibling during a 5-year period were compared to those who were treated with chemotherapy and survived at least 3 months after remission. All patients were observed for more than 2 years after diagnosis or relapse. All 11 children with acute myeloid leukemia in first remission who underwent BMT survived compared to only 1 of 15 treated with chemotherapy (p less than 0.001). In children with acute lymphoblastic leukemia (ALL), those relapsing while on chemotherapy and treated with BMT in second to fourth remission (n = 16) had a 5-year survival of 43% compared to 16% for those treated with chemotherapy (n = 53, p less than 0.05). In children with ALL relapsing after cessation of therapy, 4-year survival was 33% for BMT (n = 6) and 55% for chemotherapy (n = 15), p = 0.05).

Actuarial Analysis↗

Pharmacokinetics of streptomycin in Ethiopian children with tuberculosis and of different nutritional status.

Fifty-six malnourished Ethiopian children with tuberculosis classified in four nutritional groups (normal, underweight, marasmus and kwashiorkor), were given streptomycin 20 or 30 mg.kg-1 i.m. The plasma concentration-time data revealed an increased apparent volume of distribution in children with kwashiorkor compared to normals. The total plasma clearance was low and did not differ between the nutritional groups. Thus, the half-life was prolonged only in kwashiorkor. The results could be explained by decreased protein binding in plasma and decreased renal clearance by glomerular filtration.

Child↗

Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine.

The pharmacokinetics and bioavailability of N-acetylcysteine (NAC) have been determined after its intravenous and oral administration to 6 healthy volunteers. According to a randomized cross-over design each subject received NAC 200 mg i.v. and 400 mg p.o., and blood samples were collected for 30 h. Reduced NAC had a volume of distribution (VSS) of 0.59 l.kg-1 and a plasma clearance of 0.84 l.h-1.kg-1. The terminal half-life after intravenous administration was 1.95 h. The oral bioavailability was 4.0%. Based on total NAC concentration, its volume of distribution (VSS) was 0.47 l.kg-1 and its plasma clearance was 0.11 l.h-1.kg-1. The terminal half-life was 5.58 h after intravenous administration and 6.25 h after oral administration. Oral bioavailability of total NAC was 9.1%.

Acetylcysteine↗