Search PubMed⌕ Search

Biomedical subjects

R Lam

Publications and source records attributed to R Lam.

At least 19 recordsLinked to original sources

Solid-state coordination chemistry: structural influences of copper-phenanthroline subunits on oxovanadium organophosphonate phases. hydrothermal synthesis and structural characterization of the two-dimensional materials [Cu(phen)(VO)(O3PCH2PO3)(H2O)], [[Cu(phen)]2(V2O5)(O3PCH2CH2PO3)], and [[Cu(phen)]2(V3O5)(O3PCH2CH2CH2PO3)2(H2O)] and the three-dimensional phase [[Cu(phen)]2(V3O5)(O3PCH2PO3)2(H2O)].

The hydrothermal reactions of CuCl2*2H2O, Na3VO4, 1,10-phenanthroline, and the appropriate organodiphosphonate ligand yield [Cu(phen)(VO)(O3PCH2PO3)(H2O)] (1), [[Cu(phen)]2(V2O5)(O3PCH2CH2PO3)] (2), [[Cu(phen)]2(V3O5)(O3PCH2CH2CH2PO3)2 (H2O)] (3), and [[Cu(phen)]2(V3O5)(O3PCH2PO3)2(H2O)] (4). Compounds 1-3 exhibit two-dimensional structures. The structures exhibit distinct vanadium building blocks: square pyramidal, mononuclear V(IV) sites in 1, a binuclear unit of corner-sharing V(V) tetrahedra in 2, and a trinuclear unit of corner-sharing V(V) square pyramids and a V(IV) octahedron in 3. The network structures of 1 and 2 are constructed from one-dimensional oxovanadium-diphosphonate chains linked by Cu(II) square pyramids into two-dimensional layers. In contrast, compound 3 exhibits a two-dimensional oxovanadium-organodiphosphonate network, with Cu(II) sites decorating the surfaces. Compound 4 is unique in exhibiting a framework structure, which may be described as a three-dimensional oxovanadium-organodiphosphonate substructure with [Cu(phen)]2+ subunits covalently attached to the surface of channels running parallel to the a-axis. The magnetic properties of 1-4 are also correlated to the structural characteristics. The magnetic behavior of 2 is thus dominated by antiferromagnetic interactions. The magnetic behavior of 1 and 4 is consistent with the presence of two distinct paramagnetic metal ions, Cu(II) and V(IV). In contrast, 3 does not exhibit ferrimagnetic behavior, but rather weak antiferromagnetic coupling. Crystal data: 1, C13H10N2CuP2VO8, monoclinic P2(1)/c, a = 9.0656(5) A, b = 8.6584(5) A, c = 20.934(1) A, beta = 97.306(1) degrees, Z = 4; 2, C26H20N4Cu2P2V2O11, triclinic P1, a = 10.6096(5) A, b = 11.6951(5) A, c = 13.1796(6) A, alpha = 71.369(1) degrees, beta = 70.790(1) degrees, gamma = 80.738(1) degrees, Z = 2; 3, C30H28N4Cu2P4V3O18, triclinic P1, a = 9.4356(6) A, b = 10.6556(6) A, c = 11.0354(7) A, alpha = 118.187(1) degrees, beta = 91.416(1) degrees, gamma = 107.821(1) degrees, Z = 1; 4, C26H20N4Cu2P4V3O18, monoclinic, P2(1)/c a = 8.3947(3) A, b = 16.8401(7) A, c = 11.9144(5) A, beta = 93.903(1) degrees, Z = 2.

Journal Article↗

Using a personal digital assistant to document clinical pharmacy services in an intensive care unit.

Management Case Studies describe approaches to real-life management problems in health systems. Each installment is a brief description of a problem and how it was dealt with. The cases are intended to help readers deal with similar experiences in their own work sites. Problem solving, not hypothesis testing, is emphasized. Successful resolution of the management issue is not a criterion for publication--important lessons can be learned from failures, too.

British Columbia↗

Cytogenetic investigation of fetuses and infants conceived through intracytoplasmic sperm injection.

OBJECTIVE: To determine the incidence of aneuploidy among fetuses and infants conceived through intracytoplasmic sperm injection (ICSI) in our clinic using umbilical cord blood samples. DESIGN: Follow-up study of the cytogenetic outcome of ICSI pregnancies. SETTING: University-based IVF clinic. PATIENT(S): Forty-six couples who underwent ICSI and conceived. INTERVENTION(S): Umbilical cord blood was taken after delivery of the infant for analysis. Samples of chorionic villi and chorion were taken for studies on the spontaneous abortuses. Amniocentesis was performed for couples that chose prenatal diagnosis. MAIN OUTCOME MEASURE(S): The cytogenetic chromosomal status of the pregnancy outcome. RESULT(S): Fifty pregnancies and 55 live births were recorded, with nine spontaneous abortions. Of 43 separate umbilical cord blood samples analyzed, 1 abnormality (2%) was found, 45, XX,+21. Nine births went through prenatal diagnosis alone, with four accepting both forms of analysis-no abnormalities were found. Origin of abnormality was established in two spontaneous abortion cases (45, XO and 45, XY,-21), and the maternal chromosome was lost in both cases. CONCLUSION(S): Using umbilical cord blood obtained after birth, we obtained karyotype results from 78% of the ICSI population in our clinic. Combined with results from five additional cases that underwent prenatal diagnosis but not umbilical cord blood sampling, a chromosomal result was obtained in 87% of our ICSI population. The use of umbilical cord blood for cytogenetic analysis substantially improves the ability to determine rates of chromosomal abnormalities in newborns produced via ICSI clinics.

Adult↗

Effect of ranitidine on the pharmacokinetics of triazolam and alpha-hydroxytriazolam in both young (19-60 years) and older (61-78 years) people.

OBJECTIVE: This study evaluated the effect of oral ranitidine (75 mg and 150 mg) on the pharmacokinetics of triazolam (0.25 mg) and its major metabolite, alpha-hydroxytriazolam, in both young and older people. Metabolite data were used to distinguish the mechanism of this interaction. METHOD: This was a randomized, open-label, 3-way crossover study. Eighteen young (19-60 years) and 12 older (61-78 years) men and women were randomly assigned to receive evening doses of triazolam 0.25 mg (1) alone, (2) on the third day of dosing ranitidine 75 mg twice daily for 4 days, and (3) on the third day of dosing ranitidine 150 mg twice daily for 4 days. RESULTS: In the young group, mean triazolam area under the concentration-time curve from time zero to infinity [AUC(0-infinity)] was 10% and 28% higher after treatment with 75 mg and 150 mg ranitidine, respectively. In the older group, mean triazolam AUC(0-infinity) was 31% and 28% higher after treatment with 75 mg and 150 mg ranitidine, respectively. There was no change in the alpha-hydroxytriazolam/triazolam AUC(0-infinity) ratio in either age group, indicating that neither formation nor elimination of alpha-hydroxytriazolam was affected by ranitidine. There were no changes in the half-life of triazolam or alpha-hydroxytriazolam. CONCLUSION: Ranitidine increases oral absorption of triazolam in both young and older people. This effect is likely caused by elevation of gastrointestinal pH, allowing for greater absorption of acid-labile triazolam. The difference in this effect between age groups at the lower 75-mg dose of ranitidine suggests that older people may be more sensitive to the antisecretory effect of ranitidine.

Administration, Oral↗

Maternal origin of monosomy 21 derived from ICSI.

With the worldwide diffusion of the intracytoplasmic sperm injection (ICSI) procedure in recent years, the issue of possible genetic risks of this new and powerful technique has attracted considerable attention. An important concern is whether ICSI facilitated the passage of genetic defects from spermatozoa to offspring. ICSI was performed with spermatozoa from a frozen-thawed sperm sample from a testicular sperm extraction (TESE) of a 38 year old man who suffered from azoospermia. His wife was 36 years old. The resulting pregnancy spontaneously aborted at 8 weeks gestation after embryo replacement. Cytogenetic investigation displayed monosomy 21. The paternal origin of the single chromosome 21 was determined by molecular analysis. The segregation error leading to loss of one chromosome 21 is likely to have occurred during oogenesis rather than as a direct consequence of ICSI. Nonetheless, monosomy 21 is extremely rare and it cannot be excluded that ICSI assisted the fertilization of an abnormal oocyte.

Abortion, Spontaneous↗

Heterogeneity in systemic availability of ondansetron and granisetron following oral administration.

This open-label, randomized, two-way crossover study compared the relative heterogeneity in systemic availability of oral ondansetron and granisetron. It was conducted in 10 healthy male and 10 healthy female subjects aged 18 to 50 years. Following an overnight fast, each subject received 8 mg ondansetron and 1 mg granisetron. Treatments were separated by 7 days. Blood samples for drug assay were collected over a period of 36 h and variability in pharmacokinetic parameter estimates were assessed following standardization by their respective means. Granisetron showed significantly more variability than ondansetron in the three primary endpoints of the area under the curve extrapolated to infinite time, the area under the curve to the last quantifiable time point, and maximal concentration (p =.0032,.0037, and.0042, respectively). In one subject, concentrations of granisetron were detectable but below the lower limit of quantitation at any time point. The impact this variability may have on therapeutic efficacy is not clear. An apparent bimodal distribution in granisetron AUC infinite, which appeared to be related to smoking was observed. Because granisetron has been reported to be metabolized primarily by the cytochrome P-450 (CYP) 3A isozyme family in humans, it is possible that cigarette smoke could be an inducer of CYP3A or that CYP1A2, also implicated in the metabolism of granisetron and known to be induced by smoking, is more important in the biotransformation of granisetron than previously thought.

Administration, Oral↗

A Canadian multicenter study of three fixed doses of controlled-release ipsapirone in outpatients with moderate to severe major depression.

Ipsapirone, an azapirone with 5-hydroxytryptamine (5-HT1A) partial agonist activity, has been shown in preliminary studies to be effective in the treatment of major depressive disorder. This 8-week, randomized, double-blind study compared the efficacy, safety, and tolerability of three fixed doses of controlled-release ipsapirone (10-, 30-, and 50-mg dose once daily) with placebo in 410 patients with moderate to severe major depression (Hamilton Rating Scale for Depression [HAM-D] score > or = 20). The 10-mg ipsapirone treatment arm was discontinued early in the study. A total of 390 patients were eligible for evaluation in the intent-to-treat sample. The primary efficacy variable was the change in HAM-D total score from baseline to visit 8. There was no significant difference in efficacy in the two treatment groups versus the placebo group. The overall treatment response, defined as a 50% decrease in the HAM-D total score from baseline, was 43% with ipsapirone 50 mg given once daily, 34% with ipsapirone 30 mg given once daily, and 35% with placebo. In subanalyses, ipsapirone 50 mg given once daily was superior to placebo according to the HAM-D Core Depression (mood, guilt, interest, psychomotor activity) subtotal (p = 0.0453) and Melancholic item (p = 0.0225). Ipsapirone 30 mg given once daily was superior to placebo only in patients with moderate depression (baseline HAM-D total score < or = 25; p = 0.0100). The most common adverse effect in all groups was headache. The only dose-dependent adverse effects were dizziness and nausea.

Adolescent↗

Mood Disorder Service Genetic Database: morbidity risks for mood disorders in 3,942 first-degree relatives of 671 index cases with single depression, recurrent depression, bipolar I, or bipolar II.

There is increasing evidence that genetic factors play a role in the etiology of mood disorders. As a result, relatives of affected individuals are more often asking about their own risks to develop a mood disorder. From 1988 to 1990, all consecutive, unrelated inpatients and outpatients (index cases) presenting to the Mood Disorders Service, Department of Psychiatry, University of British Columbia, had detailed family histories taken, thus creating the Mood Disorders Service Genetic Database. Diagnoses for index cases and their first-degree relatives were made according to Research Diagnostic Criteria and Family History Research Diagnostic Criteria respectively. Morbidity risks for mood disorders were calculated for first-degree relatives (parents, siblings, children--aged 10 and above) of all index cases with a diagnosis of single depression, recurrent depression, bipolar I, or bipolar II disorder. Morbidity risks were calculated using the maximum likelihood approach. Morbidity risk data are presented according to the sex and diagnosis for the index case in an easy reference format for risk counselling. The risks are presented twice, including and excluding data for "high-risk" families whose genetic pedigree is suggestive of "autosomal dominant" inheritance.

Age of Onset↗

Some properties of hemoglobin A2.

While no significant physiologic function of hemoglobin A2 (Hb A2), the minor basic component of human hemoglobin, has been recognized, only its oxygen equilibria have been studied in detail. Since hemoglobin A2 and its oxidative denaturation product, hemichrome A2, bind to the red cell membrane, particularly to band 3, to a greater extent than do Hb A or hemichrome A, some of the properties of Hb A2 that might influence hemoglobin-membrane association were examined. Hemoglobin A2 exhibited slightly increased susceptibility to autoxidation to methemoglobin. No differences were noted between methemoglobins A and A2, including the rates of enzymatic reduction and stability of the heme-globin linkage. Oxyhemoglobin A2 had a slightly lower solubility in phosphate buffer than did hemoglobin A. While the hemichromes (prepared with phenylhydrazine) of hemoglobins A2 and A had the same optical spectra, the A2 hemichrome exhibited greater stability. It is suggested that the differences in products of oxidative denaturation may provide the basis for functional differences between hemoglobins A2 and A.

Drug Stability↗

Ovine maternal and fetal renal vasopressin receptor response to maternal dehydration.

OBJECTIVE: Arginine vasopressin secretion increases in response to increased plasma osmolality or hypovolemia. Dehydration-induced increases in plasma arginine vasopressin levels have been shown to down-regulate arginine vasopressin V2 receptors in adult rat kidneys. Our study determined ovine maternal and fetal renal arginine vasopressin receptor characteristics and receptor response to maternal dehydration. STUDY DESIGN: Eight pregnant ewes (113 +/- 1 days) were dehydrated for 72 hours; eight animals served as controls. Renal medullary tissue was isolated from maternal and fetal kidneys, and arginine vasopressin receptor characteristics determined with saturation and competition assays using tritiated arginine vasopressin, arginine vasopressin, and arginine vasopressin analogs. RESULTS: Euhydrated maternal and fetal renal medullary arginine vasopressin receptor dissociation constant (3.0 +/- 0.3 and 1.9 +/- 0.3 nmol/L) and maximal binding capacity (149 +/- 15 and 111 +/- 33 fmol/mg protein) values were similar. Pharmacologic profiles with selective agonists indicated a predominance of V2 receptors. Dehydration significantly increased maternal and fetal plasma osmolalities (304 +/- 2 to 320 +/- 2; 296 +/- 1 to 319 +/- 3 mOsm/kg water, respectively) and arginine vasopressin levels (3.8 +/- 1.4 to 29.3 +/- 4.6; 4.4 +/- 1.0 to 16.9 +/- 5.0 pg/ml, respectively) but had no effect on arginine vasopressin receptor binding. CONCLUSION: Specific, saturable, single-site tritiated arginine vasopressin binding is present in ovine maternal and fetal renal medullary membranes. Ovine maternal and fetal renal arginine vasopressin receptors do not down-regulate in response to dehydration-induced elevations in plasma arginine vasopressin levels.

Animals↗

Epidermal growth factor prohormone is secreted in human urine.

Examination of adult human urine by immunoblot analysis with antiserum specific to human recombinant 6-kDa epidermal growth factor (EGF) reveals the presence of an immunoreactive protein with a molecular mass of 165 kDa. This protein is consistently found in the morning (first) but not in day urine of adult males and females. Day urine contains variable proportions of four other high-molecular-weight EGFs with approximate molecular masses of 97, 66, 50, and 42 kDa. The 165-kDa EGF immunoreactive protein reacts with mouse amino-terminal EGF prohormone (proEGF) antiserum and comigrates with mouse urinary proEGF, suggesting that the protein is the human EGF prohormone. The 165-kDa human proEGF exhibits strong binding affinity to concanavalin A, indicating that it is glycosylated. Immunoblotting of urine in infants and children of various age groups demonstrates the presence of proEGF in all age groups, but its concentration is highest in children 2-4 yr of age. These findings, taken together with secretion of proEGF of similar molecular mass in mouse and rat urine, suggest that renal proEGF secretion is an evolutionarily conserved phenomenon and may have an important function or functions distal to the site of its synthesis.

Adult↗

Identification of pro-epidermal growth factor and high molecular weight epidermal growth factors in adult mouse urine.

By use of immunoblot analysis, we demonstrate the presence of a pro-Epidermal growth factor (EGF) with an approximate molecular weight of 165 kDa in adult mouse urine. In addition, urine contains four high molecular weight EGFs with approximate molecular weights of 116, 97, 66 and 56 kDa. The 165 kDa pro-EGF as well as the 66 and 56 kDa EGFs also are detectable in mouse kidney extract. Neither urine nor kidney contain the mature EGF of 6 kDa. The 165 kDa pro-EGF is the major product synthesized in renal tissue and secreted in urine. The finding of high molecular weight EGFs in urine suggests that part of pro-EGF secreted into urine undergoes partial proteolysis distal to its site of synthesis.

Animals↗

The nature of cytoplasmic vacuoles in chordoma cells. A correlative enzyme and electron microscopic histochemical study.

Enzyme histochemical study revealed that a sacrococcygeal chordoma not only was rich in oxidoreductive enzymes but also in the enzymes (phosphorylase, hexokinase, phosphoglucomutase, glucose phosphate isomerase and UDP-glucose dehydrogenase) leading to the synthesis of stromal glycosaminoglycans from glycogen. UDP-glucose dehydrogenase is particularly important in oxidizing UDP-glucose to UDP-glucuronic acid, the building block of hyaluronic acid and chondroitin sulfates. These enzymatic activities were consistent with the ultrastructural findings of abundant membrane-bound glycogen as well as large intracytoplasmic vacuoles with occasional residual glycogen particles. Furthermore, ultrastructural histochemical study using high iron diamine (HID) specifically localized the sulfated glycosaminoglycans (SG) extracellularly as well as intracellularly in distended Golgi saccules and 187-320 nm mature secretory vesicles. No HID staining was noted in the large intracytoplasmic vacuoles or rough endoplasmic reticulum. This study not only supports the hypothesis that the vacuoles of physaliphorous cells are the result of breakdown and utilization of membrane bound glycogen in the biosynthesis of SG, but also demonstrates that intracellular synthesis and storage of SG in chordoma are not in large vacuoles as previous investigators have believed.

Aged↗

Transforming growth factor alpha in developing rats.

Transforming growth factor-alpha (TGF-alpha) concentrations were measured in lung, brain, liver, and kidney of rats at three different ages (20 days gestation and 9 and 50 days postnatal). TGF-alpha concentrations were maximal in the lung and brain by 20 days of gestation and showed minimal changes during nursing (day 9) and young adulthood (day 50). The liver, which also showed maximal TGF-alpha concentration by 20 days of gestation, demonstrated a progressive reduction with age to nadir values in the young adult. In contrast to the pattern in other tissues, kidney had the lowest concentration of TGF-alpha in late gestation and showed an increase by 50 days of age. As TGF-alpha acts via the epidermal growth factor (EGF) receptor, its function in development may be analogous to that of EGF. Thus TGF-alpha may have a role in lung maturation and postinjury repair, liver repair and regeneration, and neuronal cell growth.

Aging↗

Effects of adrenergic agonists and adenosine on cholinergic neurotransmission in human tracheal smooth muscle.

There is only limited information available on the prejunctional regulation of acetylcholine (ACh) release from cholinergic nerves in human airway smooth muscle. Stimulation of cholinergic nerves in fresh postmortem tracheal muscle strips with electrical field stimulation (EFS) causes reproducible contractions. We have studied the effect on contractile responses of: 1) The alpha 2-adrenoceptor agonist effect of noradrenaline (NA, 0.1-30 microM) and clonidine (10 nM-30 microM), in the presence of 1 microM propranolol and prazosin +/- idazoxan (0.1 microM); 2) The beta-adrenoceptor agonist effect of fenoterol (FEN) and isoprenaline (ISO, 1 nM-30 microM) +/- ICI 118,551 (10 nM), comparing EFS responses to comparable responses to exogenous ACh; 3) The A1 and A2 adenosine receptor agonists effects of L-PIA and NECA (1 nM-10 microM). NA caused a concentration-dependent depression of the cholinergic frequency-response curve. However responses at 5 Hz were not modified by the addition of idazoxan. Similarly clonidine did not reduce contractile responses. The concentrations of isoprenaline (56 nM) and fenoterol (165 nM) required to inhibit EFS (5 Hz) by 50% (IC50) were significantly less than those required to inhibit closely matched ACh responses to a comparable degree (ISO = 117 and FEN = 304 nM), and the maximum inhibition of EFS was greater. Following isoprenaline and the beta 2-antagonist ICI 118,551 the IC50's for EFS and ACh were not different. NECA and PIA had no effect on cholinergic EFS. We conclude that a prejunctional beta 2 receptor may be present on cholinergic nerves in post-mortem tracheal smooth muscle but no evidence for alpha 2-adrenoceptor or adenosine-receptor regulation was obtained.

Adenosine↗

Idiopathic degeneration of the aortic valve: a common cause of isolated aortic regurgitation.

To establish the etiology of isolated aortic valvular regurgitation, histologic examination was carried out on 27 consecutive surgically removed aortic valves from patients with aortic regurgitation. In 12 patients, the regurgitation was due to rheumatic or syphilitic valvular disease or a congenital bicuspid aortic valve. In the remaining 15, no etiology was apparent. In the latter group, seven aortic valves were identified by the surgeon as redundant and eight as thickened and retracted. Despite these gross differences, the histologic features of the 15 valves were similar and consisted of increased and disorganized elastic and collagen fibers, with variable quantities of acid mucopolysaccharide and calcium. Although small foci of myxomatous stroma were present, they did not differ substantially from those observed in age-matched competent aortic valves removed at necropsy, nor were they as extensive as described in reports of floppy aortic valves. Idiopathic degeneration was the most common cause of aortic regurgitation, occurring in more than half of the surgically treated patients. An underlying defect in the synthesis of collagen or elastic fibers, similar to that described in mitral valve prolapse, may be an important feature in aortic valve degeneration.

Adult↗

Ovine fetal-maternal water transfer is independent of fetal prolactin levels.

To examine the effect of prolactin (PRL) on transplacental water flow, we infused mannitol (500 ml; 20% solution) over 10 min into five chronically catheterized ewes (121-134 days' gestation), producing a peak maternal plasma osmolality by 10 min and fetal osmolality by 20 min. One day before or after, an identical amount of mannitol was infused into the same ewe during the 2nd h of a 2-h infusion of PRL (40 +/- 2.2 micrograms/h) into a fetal leg vein. Mean (+/- SE) fetal plasma PRL levels were 6.9 +/- 3.2 ng/ml at baseline. Steady state fetal PRL levels were 17.7 +/- 7.4 ng/ml during PRL infusion. Maternal mannitol infused without administration of PRL to the fetus evoked a rise in fetal plasma osmolality similar to that following maternal mannitol during PRL administration to the fetus. Thus, as shown previously, PRL affects water permeability across the membranous chorioamnion, whereas results of the present study indicate that the hormone does not affect water transfer across the ovine chorionic villi (placenta).

Animals↗