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Biomedical subjects

A Chang

Publications and source records attributed to A Chang.

At least 19 recordsLinked to original sources
PubMed1992

Customised antenatal growth charts.

Charts for fetal growth do not take physiological variables into account. We have therefore designed a computer-generated antenatal chart that can be easily "customised" for each individual pregnancy, taking the mother's characteristics and birthweights from previous pregnancies into consideration. The adjusted birthweight range expected at 40 weeks' gestation is combined with a standard, longitudinal ultrasound-derived curve for intrauterine weight gain. Review at the Queen's Medical Centre, Nottingham, UK, of 4179 pregnancies with ultrasound-confirmed dates showed that, in addition to gestation and sex, maternal weight at first antenatal-clinic visit, height, ethnic group, and parity were significant determinants of birthweight in our population. Correction factors were calculated for each of these variables and entered into a computer program to adjust the normal birthweight centile limits. With adjusted centiles we found that 28% of babies conventionally designated small for gestational age (less than 10th centile) and 22% of those designated large (greater than 90th centile) were in fact within normal limits for the pregnancy. Conversely, 24% and 26% of babies identified as small or large, respectively, with adjusted centiles were "missed" by conventional unadjusted centile assessment. Adjustment for physiological variables will make assessment of fetal growth more precise and reduce unnecessary investigations, interventions, and parental anxiety.

Birth Weight↗
PubMed1992

Removing meconium from infant tracheae. What works best?

OBJECTIVE: At least nine mechanical devices are available for suctioning the tracheae of meconium-stained newborns. To our knowledge, the efficacy of these devices, as well as various suction pressures and patterns, has not been previously compared. We performed this investigation to assess these variables. DESIGN: Fourteen suction techniques (combinations of device, suction pressure, and suction intermittency) were evaluated sequentially in the trachea of each of 14 in vitro newborn piglets (1 to 4 days old); the order was randomized using a Latin square design. We chose three devices to compare: a meconium aspirator (Neotech Products Inc, Chatsworth, Calif), a hand pump (Res-Q-Vac, Repromed Systems Inc, New York, NY), and a 10F suction catheter (Superior Healthcare Group Inc, Cumberland, RI). Both the meconium aspirator and the hand pump were used with a 3.0-mm endotracheal tube. INTERVENTION: We instilled 0.8 mL of a homogeneous mixture of human meconium and saline (44 g of meconium per 100 mL of saline) in the trachea before applying each suction technique. The meconium aspirator and the suction catheter were each evaluated at three different vacuum pressures, -40, -80, and -150 mm Hg, using both continuous and interrupted suction. The hand pump was evaluated with one and two activations (one activation generates -100 cm H2O, according to the manufacturer). MEASUREMENTS AND RESULTS: The percentage of instilled meconium recovered was consistently greatest (P less than .001) with the meconium aspirator (mean, 88.9% at -150 mm Hg, 84.9% at -80 mm Hg, and 73.5% at -40 mm Hg), intermediate with the catheter (mean, 81.0% at -150 mm Hg, 73.2% at -80 mm Hg, and 67.5% at -40 mm Hg), and least for the hand pump (mean, 67.9% with one activation and 72.6% with two activations). Recovery was better with continuous suction (P = .02) and increasing pressure (P less than .001). CONCLUSIONS: Among the techniques compared, the meconium aspirator at -150 mm Hg, using continuous suction, performed best in this model. It is unknown, however, to what extent the tracheal mucosa may be affected by this degree of negative pressure.

Animals↗
PubMed1992

Prelabour rupture of the membranes at term and unfavourable cervix; a randomized placebo-controlled trial on early intervention with intravaginal prostaglandin E2 gel.

Fifty nine women with prelabour rupture of membranes, unfavourable cervix and no evidence of infection or fetal distress were randomized formally to receive prostaglandin E2 (3mg) gel or sterile K-Y Jelly intravaginally. Conservative expectant management was followed for the next 24 hours. The subsequent management of the labour followed departmental protocol. The women who received prostaglandin went into labour sooner and were delivered earlier but the duration of labour was not significantly different. There were no significant differences in other clinical outcomes. There was 1 case of uterine rupture in the prostaglandin group. We conclude that early intervention with prostaglandin E2 gel intravaginally confers no advantage compared with conservative management except for earlier confinement in this group of patients.

Administration, Intravaginal↗
PubMed1992

Activation of the contact system in lethal hypotensive bacteremia in a baboon model.

The hypotension in septicemia is believed to be mediated by the combined action of many mediators including cytokines, prostaglandins, and complement components. To evaluate the contribution of the contact/kinin-forming system to hypotension, the authors used an established experimental baboon model of bacteremia in which two concentrations of Escherichia Coli (E. coli) were used to produce lethal and nonlethal hypotension. The lethal group (n = 5) developed irreversible hypotension that significantly correlated with the decline in levels of high molecular weight kininogen (HK) and an increase in alpha 2 macroglobulin-kallikrein complexes (alpha 2M-kal). The nonlethal group (n = 9) experienced reversible hypotension, a less striking decline in HK, and only slight elevation in alpha 2M-kal. No significant changes were found in levels of factor XII, prekallikrein, and factor XI in either group. A significant change in the contact system, which reflects the fatal outcome, is the rise in alpha 2M-kal. This study suggests that irreversible hypotension correlates with prolonged activation of the contact system.

Animals↗
PubMed1992

Morphologic effects of hGRH gene expression on the pituitary, liver, and pancreas of MT-hGRH transgenic mice. An in situ hybridization analysis.

Morphologic changes in the pituitary, liver, and pancreas of mice with the metallothionein-human growth hormone--releasing hormone (MT-hGRH) transgene were analyzed by in situ hybridization histochemistry (ISH). There was progression from somatotroph hyperplasia to neoplasia in pituitaries of transgenic mice. Pituitary neoplasms were present between 9 to 12 months of age in some mice. Magnetic resonance imaging (MRI) readily identified enlarged pituitaries in MT-hGRH transgenic mice. Serum mouse GH and hGRH levels were marked elevated in MT-hGRH transgenic mice. In situ hybridization histochemistry showed mRNA for hGRH in liver, pituitary, pancreas, spleen, and in most other tissues examined. Combined ISH and immunohistochemistry in the pituitary gland showed that some of the GH cells also produced hGRH, and ultrastructural immunohistochemical analysis of pituitaries showed that GH and hGRH were localized in the same cell and within the same secretory granules. Liver cells of MT-hGRH transgenic mice showed evidence of hypertrophy, and the pancreatic islets were hyperplastic with significant increases in the islet cell areas. The morphologic changes in the liver were distinctive enough to separate control littermates from MT-hGRH transgenic mice in all cases. The enlarged pancreatic islets had increased numbers of insulin-producing cells. Immunoreactive hGRH and hGRH mRNA were both localized in islet cells, and an intense hybridization signal of hGRH mRNA, but only weak staining for hGRH protein, were detected in the liver of transgenic mice. These results indicate that excessive hGRH production leads to distinct morphologic changes in various organs in MT-hGRH transgenic mice and that there is temporal progression from hyperplasia to adenomatous somatotrophs in pituitaries with chronic stimulation by hGRH that involves paracrine, endocrine, and autocrine mechanisms.

Adenoma↗
PubMed1991

Stability of GABAA/benzodiazepine receptor alpha 1 subunit mRNA expression in reeler mouse cerebellar Purkinje cells during postnatal development.

A [35S]cRNA probe was used for the visualization of GABAA/benzodiazepine (GABAA/BZ) receptor alpha 1 subunit mRNA in developing reeler mutant mouse cerebellum. A clear hybridization signal was observed throughout the malformed reeler cerebellum from birth. Labeling was associated with Purkinje cell bodies located in three subcortical masses. Additional labeled Purkinje cells were observed within the granule cell layer and at their normal position at the interface between the molecular and granule cell layers. All reeler Purkinje cells had comparable levels of grain density, regardless of their location within the cerebellar cortex. These results indicate that Purkinje cell malpositioning, and the resulting absence of a major complement of afferents throughout development, does not impair the expression of mRNA coding for the alpha 1 subunit of the GABAA/BZ receptor.

Animals↗
PubMed1991

Catalytic triad residue mutation (Asp156----Gly) causing familial lipoprotein lipase deficiency. Co-inheritance with a nonsense mutation (Ser447----Ter) in a Turkish family.

We studied the molecular basis of familial Type I hyperlipoproteinemia in two brothers of Turkish descent who had normal plasma apolipoprotein C-II levels and undetectable plasma post-heparin lipoprotein lipase (LPL) activity. We cloned the cDNAs of LPL mRNA from adipose tissue biopsies obtained from these individuals by the polymerase chain reaction and directional cloning into M13 vectors. Direct sequencing of pools of greater than 2000 cDNA clones indicates that their LPL mRNA contains two mutations: a missense mutation changing codon 156 from GAU to GGU predicting an Asp156----Gly substitution and a nonsense mutation changing the codon for Ser447 from UCA to UGA, a stop codon, predicting a truncated LPL protein that contains 446 instead of 448 amino acid residues. Both patients were homozygous for both mutations. Analysis of genomic DNAs of the patients and their family members by the polymerase chain reaction, restriction enzyme digestion (the GAT----GGT mutation abolishes a TaqI restriction site), and allele-specific oligonucleotide hybridization confirms that the patients were homozygous for these mutations at the chromosomal level, and the clinically unaffected parents and sibling were true obligate heterozygotes for both mutations. In order to examine the functional significance of the mutations in this family, we expressed wild type and mutant LPLs in vitro using a eukaryotic expression vector. Five types of LPL proteins were produced in COS cells by transient transfection: (i) wild type LPL, (ii) Asp156----Gly mutant, (iii) Ser447----Ter mutant, (iv) Gly448----Ter mutant, and (v) Asp156----Gly/Ser447----Ter double mutant. Both LPL immunoreactive mass and enzyme activity were determined in the culture media and intracellularly. Immunoreactive LPLs were produced in all cases. The mutant LPLs, Asp156----Gly and Asp156----Gly/Ser447----Ter, were devoid of enzyme activity, indicating that the Asp156----Gly mutation is the underlying defect for the LPL deficiency in the two patients. The two mutant LPLs missing a single residue (Gly448) or a dipeptide (Ser447-Gly448) from its carboxyl terminus had normal enzyme activity. Thus, despite its conservation among all mammalian LPLs examined to date, the carboxyl terminus of LPL is not essential for enzyme activity. We further screened 224 unrelated normal Caucasians for the Ser447----Ter mutation and found 36 individuals who were heterozygous and one individual who was homozygous for this mutation, indicating that it is a sequence polymorphism of no functional significance. Human LPL shows high homology to hepatic triglyceride lipase and pancreatic lipase.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗
PubMed1991

C4b-binding protein exacerbates the host response to Escherichia coli.

Activated protein C is a plasma anticoagulant. For activated protein C to function as an anticoagulant, it must form a complex with protein S. Protein S anticoagulant activity is neutralized by formation of a reversible complex with C4b binding protein (C4bBP). C4bBP is an acute-phase plasma protein. When C4bBP levels increase, mass action forces the level of free protein S to decrease, giving rise to an acquired functional protein S deficiency. It has been proposed that these elevated C4bBP levels and the resultant acquired deficiency of protein S that occurs in inflammation could contribute to a hypercoagulable state. An experimental model to test this hypothesis was suggested by our previous studies that demonstrated that inhibition of protein C activation rendered baboons hypercoagulable in response to sublethal Escherichia coli infusion (J Clin Invest 79:918, 1987). We have extended these studies to examine the effect of inhibition of protein S activity with C4bBP in the host (baboon) response to infusion of sublethal concentrations of E coli organisms. Five sets of animals were studied: (1) those challenged with sublethal concentrations of E coli alone (0.4 x 10(10)/kg); (2) those supplemented only with C4bBP (20 mg/kg); (3) those challenged with the same level of E coli but supplemented with C4bBP (20 mg/kg); (4) those challenged with sublethal E coli and supplemented with C4bBP (20 mg/kg) and sufficient protein S (2.3 mg/kg) to fill the protein S binding sites on C4bBP; and (5) those challenged with lethal concentrations of E coli. Sublethal E coli infusion (group 1 animals) caused only an acute-phase response with no consumption of fibrinogen, detectable organ damage, or detectable tumor necrosis factor (TNF) in the plasma. C4bBP infusion (group 2 animals) resulted in no significant physiologic changes, no detectable plasma TNF, and little change in fibrinogen level. The group 3 animals, receiving both sublethal E coli and C4bBP, exhibited rapid consumption of fibrinogen, systemic organ damage, and detectable circulating TNF ultimately leading to death. The overall response of this group was very similar to the response of the group 5 animals receiving an LD100 dose of E coli. The group 4 animals, which were treated exactly as above except that C4bBP was supplemented with a slight excess of protein S, responded essentially like those that received sublethal E coli alone. These studies suggest that the elevation of C4bBP during an inflammatory response can contribute to fibrinogen consumption and vascular damage. This vascular damage may be associated with enhanced elaboration of cytokines like TNF.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Correlates of diurnal sleep patterns in infants of adolescent and adult single mothers.

Sleep behavior has been related to both child and environmental factors, but the relative importance of these factors is not yet clear. This study was an examination of the relation of diurnal sleep patterns to perinatal risk, infant temperament, home environment, parenting stress, emotional support, and social class. Twenty-three adolescent and 23 single adult mothers and infants were assessed in the home at 4 and 12 months. Percent sleep during the night was most strongly related to parenting stress and variability of night sleep to emotional support. Emotional support mediated effects of stress at 4 months. Results support the value of clinical assessment of sleep behavior.

Adaptation, Psychological↗
PubMed1991

The effect of topical retinoids on the leukotriene-B4-induced migration of polymorphonuclear leukocytes into human skin.

Systemic retinoids are effective in a variety of inflammatory dermatoses. Disorders in which polymorphonuclear leukocytes (PMN) are involved, such as psoriasis and acne, respond particularly well to various retinoids. However, side-effects restrict the use of systemic retinoids to severe manifestations. Topical application might provide the possibility of avoiding the systemic side-effects of these compounds. In this communication we report on the modulation of transepidermal migration of PMN by topical application of all-trans-retinoic acid, 13-cis-retinoic acid, arotinoid methyl sulphone and arotinoid ethyl sulphone. Test areas of healthy volunteers were pretreated with these retinoids in a cream base and with corresponding placebo creams, and intraepidermal accumulation of PMN was quantified 24 h after epicutaneous challenge with leukotriene B4 (LTB4), using elastase as a marker enzyme. Topical treatment with 13-cis-retinoic acid resulted in a marked and statistically significant inhibition of the LTB4-induced migration of PMN. All-trans-retinoic acid, arotinoid methyl sulphone and arotinoid ethyl sulphone reduced the accumulation of PMN slightly, but not statistically significantly. Topical treatment with arotinoid methyl sulphone had no effect.

Administration, Topical↗
PubMed1991

Maturation of the yeast plasma membrane [H+]ATPase involves phosphorylation during intracellular transport.

In this study we show that the plasma membrane [H+]ATPase of Saccharomyces cerevisiae is phosphorylated on multiple Ser and Thr residues in vivo. Phosphorylation occurs during the movement of newly synthesized ATPase from the ER to the cell surface, as revealed by the analysis of temperature-sensitive sec mutants blocked at successive steps of the secretory pathway. Two-dimensional phosphopeptide analysis of the ATPase indicates that, although most sites are phosphorylated at or before arrival in secretory vesicles, some phosphopeptides are unique to the plasma membrane. Phosphorylation of plasma membrane-specific site(s) is associated with increased ATPase activity during growth on glucose. Upon glucose starvation, dephosphorylation occurs concomitantly with a decrease in enzymatic activity, and both are rapidly reversed (within 2 min) upon readdition of glucose. We suggest that reversible, site-specific phosphorylation serves to adjust ATPase activity in response to nutritional signals.

Biological Transport↗
PubMed1991

Ten-year experience with cyclosporine as primary immunosuppression in recipients of renal allografts.

Cyclosporine has been used as primary immunosuppression in renal allograft recipients in our unit for the past decade. The overall clinical experience and long-term effects of the agent are reviewed. There were 461 consecutive recipients of kidney grafts; 379 received grafts from cadaver donors (CAD) and 82 from living related donors (LRD). Four separate clinical protocols were used sequentially using progressively decreasing doses of CyA; azathioprine was added in group 4 recipients of LRD grafts, and in patients receiving secondary CAD grafts (group 5). The patient mortality rate was less than 5%, with sepsis being the prime contributor. The majority of kidney grafts were lost within the first 2 months after operation; those that never functioned were found almost invariably to have been irreversibly rejected. During the subsequent years of follow-up, attrition of CAD grafts was significantly greater than LRD grafts. In contrast, the attrition rate of primary and secondary CAD grafts was the same after the first 3 months, emphasizing the importance of early immunologic graft destruction. Primary nonfunction occurred in 49% of CAD kidneys and 17% of LRD grafts; however 71% of initially nonfunctioning LRD grafts never functioned at all compared to 34% of CAD grafts, the majority of such organs undergoing fulminate rejection. Individual graft loss after 1 year was almost inevitably due to chronic rejection; there were no differences in long-term allograft function among the treatment groups. Although CyA has improved overall results of kidney transplantation, chronic rejection remains a major unresolved problem.

Adult↗
PubMed1991

Puerperal haematomas.

Forty-seven out of 31,628 patients delivered in our hospital over the past 5 years developed puerperal genital tract haematomas. Four cases, representing different types of haematoma which required different managements, were presented to illustrate this problem. A literature review was also made.

Adult↗