Biomedical subjects

K Anderson

Publications and source records attributed to K Anderson.

At least 19 recordsLinked to original sources

PubMed1992

Indium-111 monoclonal antibody B72.3 scintigraphy in colorectal cancer. Correlation with computed tomography, surgery, histopathology, immunohistology, and human immune response.

As part of an open-labeled nonrandomized multi-institutional Phase III study, the authors compared the results of In-111 (In-111) B72.3 glycyl-tyrosyl-n-diethylenetriaminepentaacetic acid lysine (GYK-DTPA) monoclonal antibody scintigraphy with computed tomography (CT), surgery, histopathology, immunohistology, and human antibody response in 23 patients with primary colorectal carcinoma. There were no significant adverse reactions to 1 mg of In-111-labeled antibody. Planar imaging identified 16 of 23 primary colon lesions, whereas single photon emission computer tomography (SPECT) imaging identified 21. SPECT also correctly identified lymphatic involvement in four patients. (There were two false-positive results.) Liver metastases were identified with SPECT imaging. Twenty-six percent of patients developed human anti-mouse antibody (HAMA). These preliminary results demonstrate that In-111 B72.3 GYK-DTPA is a safe monoclonal antibody conjugate that has a high sensitivity for identifying primary colorectal cancer. Regional lymphatic and distant liver metastases also can be imaged, but false-positive results can occur.

Adenocarcinoma↗

PubMed1992

White blood cell count and cardiovascular disease. Insights from the Framingham Study.

OBJECTIVE: To examine the relation of white blood cell (WBC) count to the development of cardiovascular disease (CVD), including coronary heart disease, stroke, peripheral arterial disease, and cardiac failure. Traditional CVD risk factors, hematocrit, and vital capacity were considered. DESIGN: Prospective cohort analysis with one baseline examination of relevant risk factors and 12 years of follow-up for CVD. PARTICIPANTS AND METHODS: A community-based sample (Farmingham Offspring Study) of 1393 men and 1401 women who were free of CVD at the onset of the study and who were between the ages of 30 and 59 years at baseline. Time-dependent multiple variable logistic regression methods were used. RESULTS: There were 180 CVD events in men and 80 in women. The WBC count was correlated most strongly with the number of cigarettes smoked per day, hematocrit, and vital capacity. Among nonsmoking men with WBC counts within the normal range, the age-adjusted WBC count was significantly associated with CVD and coronary heart disease incidence. For each 1.0 x 10(9)/L-cell difference in WBC count, the CVD risk increased 32%. In women, each 1.0 x 10(9)/L-cell increment in WBC count was associated with a 17% increase in CVD risk, but only in smokers, and the relationship was not statistically significant after adjustment for relevant risk factors. CONCLUSIONS: The degree of elevation of WBC count within the normal range is a marker for increased risk of CVD that is partially explained by cigarette smoking. Future studies should include differential WBC determinations to assess their association with CVD.

Adult↗

PubMed1992

Molecular cloning of cDNAs for the human granulocyte colony-stimulating factor receptor from HL-60 and mapping of the gene to chromosome region 1p32-34.

Early studies examining the effects of purified or recombinant granulocyte colony-stimulating factor (G-CSF) on human leukemia cell lines demonstrated that some cell lines, such as HL-60, could be induced to differentiate in response to G-CSF. In two recent studies reporting the cloning of the human G-CSF receptor (hGCSFR), four classes of receptor cDNA were identified and, surprisingly, the message for this receptor was reportedly expressed by HL-60 at either very low levels or not at all. Using a mouse G-CSF receptor probe, we cloned and sequenced a cDNA for hGCSFR from an HL-60 cDNA library in plasmid and used it to identify 31 additional clones from an HL-60 cDNA library in phage. Polymerase chain reaction analysis of the 31 phage clones established that 29 were derived from class I hGCSFR mRNA, one was derived from class III mRNA, and one was derived from class IV mRNA. In addition, the hGCSFR gene was chromosomally localized by Southern blot analysis of its segregation pattern in a panel of rodent-human hybrid DNAs using the radiolabeled cDNA probe. The hGCSFR locus was present in hybrids retaining the distal short arm of human chromosome 1 and absent in hybrids that did not retain this region. Chromosomal in situ hybridization refined the localization of the hGCSFR gene to region 1p32-p34. The combination of hybrid DNA analysis and in situ hybridization places the hGCSFR gene telomeric to the CSF1, JUN, and TCL-5 loci.

Base Sequence↗

PubMed1992

A unique factor XIII inhibitor to a fibrin-binding site on factor XIIIA.

An 81-year-old woman, who presented with sudden episodes of spontaneous bleeding, was found to have a specific inhibitor of factor XIII. Her fibrin clots had approximately 70% gamma-gamma and no alpha polymer formation, under conditions where normal fibrin was fully cross-linked; the patient's clots were soluble in urea or monochloroacetic acid. Factor XIII activity in her plasma was 24%, measured by the dansylcadaverine incorporation assay. When mixed with normal plasma, the patient's plasma inhibited fibrin cross-linking; however, in mixtures of patient and normal plasma, there was no inhibition of factor XIII activity when assayed by the incorporation of dansylcadaverine into casein. Thus, this inhibitor was active against fibrin cross-linking but not against ligation of small molecules to casein. Consequently, gel electrophoresis of reduced, sodium dodecyl sulfate-solubilized fibrin clots was a simple, quantitative method that was used to measure inhibitor activity. This inhibitor is unique and has been designated inhibitor New Haven. It was neutralized by anti-IgG and anti-kappa. It did not inhibit the activation of factor XIII but did inhibit fibrin cross-linking. There was complex formation between the inhibitor and activated factor XIII (A', A*) but not between A2 or fibrinogen. Only A', A* and the 56-Kd fragment bound to affinity columns made with this IgG. The inhibitor significantly decreased the binding of A', A* to fibrin clots. These data indicate that the epitope for this inhibitor is in a fibrin binding site. It is hidden in the zymogen and expressed on A' and A*, indicating that the conformational change occurring with the cleavage of the activation peptide is sufficient to expose the fibrin binding site.

Aged↗

PubMed1992

Inositol lipids and phosphates in the proliferation and differentiation of lymphocytes and myeloid cells.

It is established that receptor-stimulated hydrolysis of phosphatidylinositol 4,5-bisphosphate is an essential signalling reaction in the responses of many haemopoietic cells to stimuli: examples include platelet activation, antigen-driven initiation of cell proliferation in mature B and T lymphocytes and histamine release by mast cells, and chemotaxis and oxygen radical generation by neutrophils. However, the roles of inositol lipids and phosphates in the development of haemopoietic and immune cells are less well understood. This paper discusses three such situations: the sequential employment of phosphatidylinositol 4,5-bisphosphate hydrolysis and cyclic AMP accumulation as two signals essential to the action of the B lymphocyte-stimulatory cytokine interleukin 4; the involvement of antigen receptor-triggered inositol lipid hydrolysis in apoptotic elimination of immature anti-self T lymphocytes in the fetal mouse thymus; and the possible role of changes in the levels of abundant inositol polyphosphates in the differentiation of HL-60 promyelocytic cells and of normal human myeloid blast cells.

Bone Marrow Cells↗

PubMed1992

Species differences in the immunoreactive patterns of calcitonin gene-related peptide in the pancreas.

In the pancreas, calcitonin gene-related peptide (CGRP) immunoreactivity has been described in nerve fibers and in distinct types of islet cells. This unique, apparently species-specific cell-type expression prompted the present investigation to clarify further the pattern of CGRP immunoreactivity in different mammalian species (i.e., different strains of rats, mice, guinea pigs, rabbits, cats, dogs, pigs, and humans) commonly used for functional and anatomical studies of the pancreas by means of immunohistochemistry using three different CGRP antibodies. In each species, CGRP-immunoreactive neurites innervate the exocrine and endocrine compartments, the vasculature, and the intrapancreatic ganglia, where they form dense networks encircling unstained cell bodies. The only exception is the pig pancreas, where the islets appear to be devoid of immunoreactive fibers. The overall density of immunoreactive pancreatic axons in different species is as follows: rat, mouse, and rabbit greater than guinea pig greater than or equal to pig and cat much greater than dog and human. CGRP-immunoreactive endocrine cells appear to be restricted to the rat pancreas, where they form a subpopulation of somatostatin-containing D cells. In contrast, in mouse, guinea pig, cat, dog, and human pancreas, a homogeneous staining of the core of the islets, where insulin-producing B cells are located, was visualized in sections incubated with the rabbit CGRP antiserum at 4 degrees C, but not at 37 degrees C (an incubation temperature that does not affect the islet cell staining in the rat nor the fiber labeling in any species). Furthermore, the staining of islet B cells was not reproducible with all the CGRP antibodies used, all of which comparably stain nerve fibers in each species, and islet D cells in the rat. Immunoreactive islet cells were not visualized in pig and rabbit pancreas. These results are consistent with the hypothesis that the expression of CGRP in nerve fibers is a common feature of mammalian pancreas, whereas its expression in endocrine cells appears to be restricted to the D cells of the rat pancreas.

Animals↗

PubMed1992

Pancreatoduodenectomy with preservation of the stomach and pylorus: a safe and effective alternative in children.

The time-honored surgical approach to resectable tumors of the head of the pancreas or distal common bile duct has been a Whipple operation for adults and children. In recent years, pylorus-preserving pancreatoduodenectomy has been used for adults. The postoperative physiological advantages may be enhanced in children, and for this reason the pylorus-sparing approach was used in a 15-year-old girl with a tumor of the distal common duct. The pylorus-preserving pancreatoduodenectomy was safe and effective in this patient and should be considered for children with resectable tumors of the distal common bile duct and pancreatic head.

Adolescent↗

PubMed1992

Polylactosaminoglycan modification of the respiratory syncytial virus small hydrophobic (SH) protein: a conserved feature among human and bovine respiratory syncytial viruses.

We investigated the nature of the oligosaccharide modification of the glycosylated forms of the small hydrophobic integral membrane protein, SH (previously designated 1A), of respiratory syncytial (RS) virus. Analysis of SH protein expressed in cells infected with RS virus or with a recombinant vaccinia virus revealed two glycosylated SH protein species, SHg and SHp, which contained N-linked carbohydrate residues. SHp migrated diffusely on polyacrylamide gels, which suggested modification by polylactosaminoglycan oligosaccharides. Polylactosaminoglycan modification of SHp was established from three lines of investigation: (1) the synthesis of SHp in a cell line (IdID) conditionally defective in the ability to add specific carbohydrate residues to N- or O-linked oligosaccharide chains required the addition of galactose, which is a component of the N-acetyllactosamine repeating unit; (2) SHp was sensitive to digestion with endo-beta-galactosidase, which cleaves the beta 1-4 linkage between galactose and N-acetylglucosamine of the repeated N-acetyllactosamine subunit; and (3) SHp was selected by Datura stramonium lectin (Dsl), which has specificity for polylactosaminoglycans. The presence of SHp as a component of purified human subgroups A and B and bovine RS virus particles was demonstrated by Dsl affinity selection. In addition to SHp, nonglycosylated SHo was selected by Dsl affinity, indicating that SHp and SHo may associate to form complexes within infected cells and virus particles. To identify conserved amino acid residues among the human and bovine SH glycoproteins that may function as signals for polylactosaminoglycan modification, the nucleotide sequences of the SH protein genes of a human subgroup B virus (8/60) and a bovine virus (391-2) were determined and compared to those of a human subgroup A virus (A2), a subgroup B virus (18537), and a bovine virus (A51908). A comparison of the deduced amino acid sequences of the human and bovine RS virus SH proteins indicated that a central hydrophobic region and the presence of potential N-linked glycosylation sites on either side of the central hydrophobic region were conserved features that may be required for the polylactosaminoglycan modification of SH.

Amino Acid Sequence↗

PubMed1992

Molecular and structural basis of hemagglutination in mengovirus.

The molecular and structural basis of mengovirus hemagglutination (HA) was investigated by the comparison of nucleotide sequences of the entire capsid coding regions of an HA+ variant, two HA- mutants, 205 and 280, and two HA+ revertants of 205. The mutants were selected after acridine mutagenesis of mengovirus-37A, a heat-stable and HA+ variant that is neurotropic in mice. HA+ revertants of mutant 205 were isolated from brain tissue of mice inoculated with mutant 205. The nucleotide sequences were determined by consensus RNA sequencing using genomic RNA templates from purified virions. Two nucleotide differences were observed in the VP1 coding region of the RNA genomes of mutants 205 and 280 in comparison to the RNA sequences of 37A and the revertants. Interpretation of these data predict substitutions of two consecutive amino acids at residues 1231 (K to R) and 1232 (P to S) of VP1 which form part of the H-I loop of VP1 found at the icosahedral fivefold axis. Analysis of the amino acid substitutions in the context of the three-dimensional structure of the mengovirus-M capsid indicated that hemagglutination most likely involves residues found at the icosahedral fivefold axis and probably does not involve the residues that form the putative cellular receptor binding site (the "pit"). Eleven amino acid differences were observed between the structural proteins of mengovirus-M and 37A, five in VP1, three in VP2, and three in VP3.

Amino Acid Sequence↗

PubMed1992

The surgical management of infants and children with ambiguous genitalia. Lessons learned from 25 years.

Over a 25-year period, 91 children with ambiguous genitalia have received surgical management. Female sex assignment was made for 79. Of these, 60 patients underwent extensive clitoral reconstruction consonant with the female assignment. Forty-two patients had vaginal reconstruction. Factors relating to success include: (1) prompt and appropriate sex assignment; (2) early and accurate diagnosis; (3) conservative reconstruction of the clitoris at an early age (less than 1 year); and (4) choice of vaginal reconstruction based on the severity of the malformation. Long-term follow-up demonstrates satisfactory anatomic and functional results when clitoral surgery alone was required. Functional results for patients with extensive vaginal reconstruction have been compromised. Physicians caring for children with congenital intersexual anomalies can expect to encounter a wide spectrum of anatomic and physiologic derangements. Cosmetic appearance alone is an inadequate measure of success because endocrinologic, social, psychological, and sexual factors must be blended into comprehensive evaluation of these patients. The management plan must be flexible and individualized, incorporating long-term follow-up to adulthood.

Clitoris↗

PubMed1992

A pilot study of the relationship between experts' ratings and scores generated by the NBME's Computer-Based Examination System.

This pilot study evaluates the consistency of experts' ratings of students' performances on the National Board of Medical Examiners' Computer Based Examination (CBX) cases and the relationship of those ratings to the CBX's scoring algorithm. The authors were investigating whether an automated scoring algorithm can adequately assess an examinee's management of a computer-simulated patient. In 1989-90, at the Michigan State University College of Human Medicine, eight students, completing a surgery clerkship, each managed eight CBX cases and took a computer-administered, multiple-choice examination. Six clerkship coordinators rated the students' performances in terms of overall management, efficiency, and dangerous actions. The ratings correlated highly with scores produced by the CBX's scoring system.

Algorithms↗

PubMed1992

Plasma vitamin E concentrations of older infants fed cow's milk or infant formula.

Nutrition of older infants, though important for optimal brain development, is inadequately studied. The beverage choice markedly influences nutrient intake, but little is known regarding nutrition status of older infants, particularly for vitamin E. This study assessed vitamin E intakes and plasma tocopherol concentrations in two groups of healthy infants, 8 to 13 months of age, who had consumed either cow's milk (n = 45) or milk-based formula (n = 55) for a minimum of the 3 preceding months. Mean (+/- SEM) vitamin E intake was significantly lower (p < or = 0.001) by the infants who had consumed cow's milk (CMF) than by infants who had consumed formula (FF); 4.1 +/- 0.25 mg/day and 10.9 +/- 0.57 mg/day, respectively. Mean (+/- SEM) intake of linoleic plus linolenic acids was significantly lower (p < or = 0.005) by CMF infants (3.4 +/- 0.2 g) than by FF infants (9.9 +/- 1.0 g), although mean (+/- SEM) dietary vitamin E to polyunsaturated fat ratio (E/PUFA ratio) was the same in both FF and CMF infants (1.3 +/- 0.1). Plasma alpha-tocopherol concentration (mean +/- SD) was significantly lower (p < or = 0.005) in CMF than in FF infants (0.86 +/- 0.28 mg/dl vs. 1.14 +/- 0.42 mg/dl, respectively). Dietary vitamin E intakes were positively correlated (p < or = 0.05) with plasma alpha-tocopherol concentrations. No correlations were found between plasma alpha-tocopherol concentrations and total fat intake, dietary E/PUFA ratios, erythrocyte polyunsaturated fatty acids > or = C18:2, or number of hours postprandial that blood was drawn.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Bovine respiratory syncytial virus nucleocapsid protein: mRNA sequence analysis and expression from recombinant vaccinia virus vectors.

The nucleotide sequence of the mRNA encoding the nucleocapsid (N) protein of bovine respiratory syncytial (BRS) virus, strain 391-2, was determined. Recombinant vectors containing a cDNA of the complete N gene were constructed, and expression of the N protein in eukaryotic cells was demonstrated using two different vector systems. The BRS virus N mRNA was 1197 nucleotides in length, exclusive of poly(A), and had a single major open reading frame that encoded a polypeptide of 391 amino acids with a calculated M(r) of 42.6K. The nucleotide and amino acid sequences of the BRS virus N gene were compared to those of human respiratory syncytial (HRS) virus strains A2 and 18537, and to BRS virus strain A51908. The level of nucleic acid identity between the N mRNA of BRS virus 391-2 and both HRS virus subtypes was 80 to 81%, whereas the identity between the two BRS virus strains was 97%. A 93 to 94% level of identity was observed between the deduced amino acid sequences of the N protein of BRS virus 391-2 and the corresponding sequences of the two HRS virus strains. The two BRS virus N proteins differed in amino acid sequence at only three positions. Recombinant BRS virus N protein was expressed using two different vector systems: in cells from a plasmid using the vaccinia virus/T7 polymerase expression system or from a recombinant vaccinia virus. N proteins synthesized by the two vector systems migrated with an electrophoretic mobility identical to that of authentic BRS virus N protein, and were precipitated by anti-BRS virus antibodies.

Amino Acid Sequence↗

PubMed1992

Intracellular processing of the human respiratory syncytial virus fusion glycoprotein: amino acid substitutions affecting folding, transport and cleavage.

The intracellular processing and transport of the respiratory syncytial virus (RSV) fusion (F) glycoprotein was examined by comparing the maturation and stability of wild-type F, uncleaved mutant F and chimeric F glycoproteins expressed by recombinant vaccinia viruses to that of F protein expressed by RSV. One of the recombinant viruses, vF317, expressed F protein (F317) that was processed like the RSV F glycoprotein. F317 was synthesized initially as F0, the uncleaved glycosylated precursor of mature F protein, and formed stable oligomeric structures that were maintained following cleavage of F0 to form the disulphide bond-linked F1 and F2 subunits. Most of the newly synthesized F0 expressed by either RSV or by vF317 was sensitive to treatment with endoglycosidase H (Endo H). Following cleavage of F0, F1 was resistant to Endo H, suggesting that conversion to complex-type sugars, which takes place in the medial Golgi apparatus, occurred simultaneously with or immediately prior to cleavage of F0 into F1 and F2. Another recombinant virus, vF313, synthesized only uncleaved F protein (F313) that comigrated with F0. Uncleaved F313 was expressed as a stable glycosylated protein; however, unlike cleaved F317, its oligosaccharides were not modified to complex forms, as determined from its Endo H sensitivity, and uncleaved F313 did not assemble into stable oligomeric structures. Nucleotide sequence analysis of the cDNA clones encoding F313 and F317 revealed four predicted amino acid sequence differences, none of which were located at the cleavage site. Expression of chimeric F proteins obtained by restriction fragment exchange between the two cDNA clones indicated that two amino acid changes in the F1 domain, located at amino acid residues 301 (Val to Ala) and 447 (Val to Met), resulted in the expression of uncleaved F protein. A change at either of these two amino acid residues, 301 or 447, resulted in the expression of inefficiently cleaved F protein, defining an additional F protein phenotype. Pulse-chase analyses to examine the association of recombinant F glycoproteins with gradient-purified fractionated membranes or with GRP78-BiP, a protein resident in the endoplasmic reticulum (ER) which binds to nascent proteins, revealed that uncleaved F protein (F313) is associated with GRP78-BiP in the ER for a longer time than F317, and little if any F313 was transported to the cell surface. In addition, the uncleaved F protein (F313) was not recognized by a panel of F protein-specific monoclonal antibodies in ELISA or indirect immunofluorescence assays, suggesting that F313 was misfolded and, as a result, not transported properly or cleaved.

Antigens, Viral↗

PubMed1992

Isolation of adult cardiomyocytes initiates a return of inositol trisphosphate phosphorylating activity.

1. We have previously reported that the addition of noradrenaline to [3H]-inositol-labelled adult rat atria or isolated perfused hearts caused the release of inositol-1,4,5-trisphosphate, which was metabolized by dephosphorylation to inositol-4-monophosphate. Inositol-1,3,4,5-tetrakisphosphate and its dephosphorylation products were not detected. 2. In the current study, the addition of noradrenaline to [3H]-inositol-labelled adult rat cardiomyocytes caused the release of inositol-1,4,5-trisphosphate, which was metabolized in part by phosphorylation to inositol-1,3,4,5-tetrakisphosphate. 3. These results demonstrate that the isolation and culture of rat adult cardiomyocytes initiates enhanced generation of inositol-1,3,4,5-tetrakisphosphate. This change would be expected to enhance the calcium response of the cells to stimulation of alpha 1-adrenoceptors.

Animals↗

PubMed1992

Cholinoceptor regulation of cyclic AMP levels in bovine adrenal medullary cells.

1. The regulation of adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels by cholinoceptors has been studied in cultured bovine adrenal medullary cells. 2. Acetylcholine (100 microM), nicotine (10 microM) and dimethylphenylpiperazinium (20 microM) each increased cellular cyclic AMP levels 2 to 4 fold over 5 min in the absence of phosphodiesterase inhibitors. The muscarinic agonist acetyl-beta-methylcholine (100 microM) had no effect either on its own or on the response to nicotine. The responses to acetylcholine and nicotine were unaffected by atropine (1 microM) but were abolished by mecamylamine (5 microM). 3. Cellular cyclic AMP increased transiently during continuous exposure to nicotine (1-20 microM), with the largest response seen after 5 min, a smaller response after 20 min, and no change in cyclic AMP levels seen after 90 or 180 min. The maximal response after 5 min stimulation was seen with 5-10 microM nicotine and the EC50 was about 2 microM. In contrast, extracellular cyclic AMP levels did not change after 5 or 20 min stimulation with nicotine, but increased slightly after 90 min and further after 180 min. 4. The cellular cyclic AMP response to nicotine (10 microM) was unchanged or weakly enhanced in the presence of the unselective phosphodiesterase inhibitor, isobutylmethylxanthine, and was unchanged in the presence of rolipram. Nicotine did not interact synergistically with low concentrations of forskolin. The response was however completely abolished in the absence of extracellular Ca2+.

1-Methyl-3-isobutylxanthine↗

PubMed1992

Human cytotoxic T cells stimulated by antigen on dendritic cells recognize the N, SH, F, M, 22K, and 1b proteins of respiratory syncytial virus.

We examined the human cytotoxic T-cell repertoire of nine adults to 9 of the 10 proteins of respiratory syncytial (RS) virus. Peripheral blood mononuclear cells from normal adults were stimulated with RS virus in vitro. The resulting polyclonal cultures were tested for lysis of B-lymphoblastoid cell lines infected with recombinant vaccinia viruses expressing each of nine individual RS virus proteins. The use of peripheral blood dendritic cells to present antigen gave more easily reproducible results over a shorter culture period than conventional methods. The six RS virus proteins most strongly recognized were the nucleoprotein N (nine of nine donors with greater than 10% above background lysis; P = 0.0004), the surface proteins SH (six of nine donors; P = 0.002) and F (five of nine donors; P = 0.008), the matrix proteins M (five of nine donors; P = 0.004) and 22K (three of nine donors; P = 0.01) and the nonstructural protein 1b (six of nine donors; P = 0.004). There was no significant recognition of the major surface glycoprotein G (two of nine donors), the internal phosphoprotein P (one of nine donors), or the nonstructural protein 1c (one of nine donors). Recognition was major histocompatibility complex class I restricted, but no association between major histocompatibility complex phenotype and protein specificity of T cells was seen. Recognition of F and 22K appeared to be associated with recent infection indicated by increased levels of anti-RS virus immunoglobulin G antibody in serum measured by enzyme-linked immunosorbent assay. Since cytotoxic T-cell recognition of RS virus proteins has been demonstrated to be important in the clearance of virus from infected hosts, the N, M, SH, 1b, F, and 22K proteins should be considered potential vaccine components.

Adolescent↗

PubMed1992

Intravenous pamidronate in the treatment of osteoporosis associated with corticosteroid dependent lung disease: an open pilot study.

BACKGROUND: Bisphosphonates have been shown to be effective agents in the treatment of postmenopausal osteoporosis. Because corticosteroid associated osteoporosis is often associated with increased bone turnover, the effect of intermittent intravenous infusions of pamidronate on this condition has been investigated. METHODS: Seventeen patients (five male) with chronic corticosteroid dependent lung disease (15 asthma, two sarcoidosis) were treated with infusions of 30 mg pamidronate once every three months for one year. These patients had been taking an average of 14 (range 7.5-40) mg prednisolone a day for an average of 14 (range 3-30) years. Bone density measurements, by dual energy x ray absorptiometry, and radiography of the dorsolumbar spine were carried out before and one year after treatment. Bone formation was assessed by measurement of serum alkaline phosphatase and bone resorption by measurement of the fasting urinary hydroxyproline: creatinine ratio at the same time as densitometry and radiography were performed. RESULTS: Pretreatment density of L2-4 and the neck of the femur was significantly lower in these patients compared with a cohort of 100 age and sex matched controls (L2-4 (mean (SEM)): 0.906 (0.050) g/cm2 v 1.142 (0.016) g/cm2; neck of femur: 0.793 (0.030) g/cm2 v 0.936 (0.013)) g/cm2. After treatment there was a significant fall in serum alkaline phosphatase activity from (mean (SEM)) 220 (16) U/1 to 174 (9) U/1 (normal 80-280 U/1) and in the fasting urinary hydroxyproline:creatinine ratio from (mean (SEM) 0.040 (0.006) to 0.024 (0.003) (normal < 0.033). A significant rise was noted in L2-4 density to 0.927 (0.047) g/cm2; mean rise of 3.4%). No change was noted in density of the neck of the femur. CONCLUSIONS: Intermittent infusions of intravenous pamidronate would seem to be effective in both reducing turnover of bone and increasing bone density in corticosteroid induced osteoporosis associated with chronic lung disease. Longer term controlled studies are indicated.

Adult↗