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Biomedical subjects

C Lam

Publications and source records attributed to C Lam.

At least 91 records · Page 5Linked to original sources

Sleep apnea syndrome and essential hypertension.

More than half of patients with essential hypertension have sleep apnea. The incidence of unrecognized sleep apnea in patients with essential hypertension was assessed. Twenty-three patients taking antihypertensive medication were selected at random from a hypertension clinic. They were evaluated by questionnaire for symptoms of sleep apnea, and during 3 hours of sleep, measurements were made of respiratory patterns using an impedance pneumograph, arterial O2 saturation with an ear oximeter and air flow at the mouth or nose with a face mask pneumotacograph. Abnormal sleep apneas (average 20 seconds) lasting for an average of 19% sleep time were found in 11 patients (48%). Significant arterial O2 desaturation, defined as a decrease of at least 4% and to less than 90%, was observed in 7 of these 11 (30%), with an average saturation of 87% at the end of the apneic episodes. Thus, almost one-third of patients randomly selected had significant arterial O2 desaturation during sleep because of sleep apnea, and it is suggested that sleep apnea may play a part in the development of essential hypertension.

Adult↗

Effect of subinhibitory concentrations of josamycin on the expression of M protein by group A streptococci.

In an attempt to inhibit the biosynthesis of the type-specific M protein usually expressed on surface fimbriae group A Streptococcus pyogenes delta 2305 was cultivated in Todd-Hewitt broth containing 10% human serum and subinhibitory concentrations of either josamycin, erythromycin or clindamycin. Electron microscopy revealed that the antibiotic-pretreatment had little visible effect on the surface structures of the streptococci. However, josamycin and clindamycin-pretreated bacteria adhered less to hydrophobic gels than erythromycin-pretreated or untreated control cultures. Due to the decrease in surface hydrophobicity, the drug-pretreated bacteria also activated complement more readily and fixed more C3 on their surface. Consequently the killing of josamycin and clindamycin-pretreated bacteria by polymorphonuclear leucocytes was significantly enhanced. Similar findings were obtained when the M protein was removed from the bacteria by digestion with trypsin. These results suggest that josamycin, like clindamycin, reverses the capacity of group A streptococci to resist opsonization by normal human serum and interferes with the adhesion of the organisms to host epithelial cell surfaces.

Adhesiveness↗

Differing antimicrobial potency and specificity of peripheral blood and autologous exudative polymorphonuclear leucocytes.

Little is known about the antimicrobial potency and specificity of polymorphonuclear leucocytes which actually appear at the sites of bacterial invasion in tissues. In the present work we have compared inflammatory leucocytes induced by intraperitoneal injection of casein in rabbits with autologous peripheral blood cells in killing Escherichia coli serotype 01 and Staphylococcus aureus 502A. The results indicate that inflammatory leucocytes differ significantly from their virgin blood ancestors. While the blood leucocytes were only able to suppress the growth of the gram-negative bacteria, autologous exudative cells killed more than 95% of the test organisms within 1 h of incubation at 37 degrees C. The enhanced microbicidal activity of the inflammatory cells however, was only specific for the gram-negative bacteria, as evidenced by the failure of leucocytes to kill Staph. aureus to the same extent as the peripheral blood cells. In association with the enhanced gram-negative microbicidal activity the inflammatory cells produced chemiluminescence and released two to three times more O2-anions than the peripheral cells. We interpret these observations to mean that chemotactic factors such as casein activate inflammatory cells to increase their oxidative metabolism. Since microbicidal action of leucocytes is thought to proceed in part through oxygen-dependent reactions, the inflammatory leucocytes would be expected to effectively kill bacteria that are highly susceptible to these lethal oxygen metabolites. It cannot therefore be assumed that assessment of the functional capacity of the virgin peripheral blood PMNs would provide information on the functional characteristics of activated leucocytes which actually migrate to and accumulate at inflammatory sites.

Animals↗

Therapeutic relevance of penicillin-induced hypersensitivity of Staphylococcus aureus to killing by polymorphonuclear leukocytes.

There is an overwhelming body of evidence that certain Staphylococcus aureus strains become more sensitive to killing by polymorphonuclear leukocytes after their growth in media containing subinhibitory concentrations of penicillin. However, it is not clear to what extent this phenomenon contributes to the curative effect of penicillin in vivo. To explore its therapeutic relevance, we evaluated the interaction of staphylococci pretreated with penicillin in vitro with leukocytes in cell-proof diffusion chambers (porosity, 0.22 micron) implanted subcutaneously in rabbits. Under this in vivo environment, staphylococci pretreated with penicillin remained hypersensitive to leukocyte killing as under in vitro conditions. Furthermore, when the staphylococci were mixed with the leukocytes in chambers implanted intraperitoneally in mice which subsequently received intravenously a suboptimal dose of penicillin, they also became hypersensitive to leukocytic killing. However, because the staphylococcal growth rate was considerably reduced in vivo, the degree of penicillin-induced sensitivity to leukocytic killing was smaller than that obtained in test tube cultures; nevertheless, the enhanced killing was significant. Additional support that the curative effect of penicillin partly depends on its synergistic action with the leukocytes was provided by the relative decrease in virulence of staphylococci pretreated with penicillin in mice in which the cellular host defenses were already recruited at the focus of inoculation. These observations indicate that penicillin-induced hypersensitivity of staphylococci to leukocytic killing is not only an in vitro phenomenon, but an effect which has therapeutic relevance.

Animals↗

Effect of low intraphagolysosomal pH on antimicrobial activity of antibiotics against ingested staphylococci.

The ability of aminoglycoside antibiotics and rifampicin to kill Staphylococcus aureus that had been ingested by blood polymorphonuclear leukocytes (PMNs) in vitro was investigated. Gentamicin and streptomycin failed to kill intracellular staphylococci, possibly because they could not penetrate PMNs or were inactivated by the low intraphagolysosomal pH. Rifampicin accumulated within the leukocytes in a form that killed staphylococci in a cell-free medium, but the bactericidal activity of intracellular rifampicin against ingested staphylococci was much less than that in a cell-free system. Investigations with granules isolated from PMNs, at various pH-values, revealed that the impairment of rifampicin activity was a result of limitation of the staphylococcal growth rate by a low pH. These observations indicate that the inhibition of intraphagocytic bacterial growth by the low intraphagolysosomal pH and other phagolysosomal bacteristatic factors determines the antimicrobial activity of accumulated antibiotics.

Animals↗

An evaluation of repeated injections of epinephrine for the initial treatment of acute asthma.

We evaluated 4 treatment regimens using single and multiple injections of epinephrine for the initial treatment of acute asthma in children. Twenty-five patients received 2 injections of epinephrine followed by Sus-Phrine (Group EES) given 20 min apart, 25 received Sus-Phrine only (Group S), 24 received Sus-Phrine followed by 2 placebo injections 20 min apart (Group SPP), and 14 received epinephrine only (Group E). Clinical score and pulmonary function were assessed over a 2-h period. The failure rate was similar in Groups EES, S, and SPP (combined failure rate, 17.8%). The failure rate (46%) in Group E was significantly greater (p less than 0.05). The clinical score and pulmonary function was significantly better 5 min after the first injection in Group EES than in Groups S and SPP, but no significant differences were noted thereafter. At 25 min the pulmonary function was similar whether 1 or 2 epinephrine injections were administered. The number of patients exhibiting side effects was significantly greater in the groups receiving epinephrine than in the groups receiving Sus-Phrine only (p less than 0.05). The relapse rates during the 24-h period after the emergency room treatment were similar in Groups EES, S, and SPP (combined relapse rate, 14.3%). We conclude that repeated injections of epinephrine are necessary to sustain bronchodilation but that they do not have a cumulative effect. Furthermore, there is little therapeutic advantage of these repeated injections over a single injection of Sus-Phrine for the initial treatment of acute asthma.

Acute Disease↗

Long-term sequelae of bronchiolitis induced by nitrogen dioxide in hamsters.

The long-term consequences of acute lung injury during critical growth periods of the lung were evaluated by inducing mild bronchiolitis with nitrogen dioxide (NO2) in 3-day-old (newborn) and 21-day-old (young) hamsters. Hamsters were exposed to 30 ppm NO2 for 7 days. Age-matched animals exposed to room air served as controls. Lung volumes, static deflationary pressure-volume curves, mean linear intercept, and internal surface area were measured when the animals reached 1 yr of age. Newborns exposed to NO2 showed an increased volume at 25 cm H2O pressure (V25) adjusted for body weight, a decreased transpulmonary pressure at 60% of V25, and an increased mean linear intercept when compared with control animals. The internal surface area was less than that in the control animals; the difference approached significance. In the young exposed group there were no differences for any measurements when compared with the control group. These data indicate that a mild injury imposed during the newborn period may result in physiologic and morphometric changes that simulate mild emphysema in the mature animal.

Animals↗

Pitfalls in the interpretation of serum theophylline levels.

In two groups of patients, noncompliance with drug regimens resulted in misinterpretation of serum theophylline levels. All six chronic asthmatics in the first group, found in a retrospective review of 43 outpatient charts, had outpatient serum theophylline levels in the therapeutic range (10 to 20 microgram/mL) and at least a 7-microgram/mL greater inpatient theophylline level while receiving the same dosage. When hospitalized, four of these patients had serum theophylline levels in the toxic range (greater than 20 microgram/mL). In the second group four hospitalized patients had persistently low serum theophylline levels despite an adequate theophylline dose. When compliance was enforced, serum theophylline levels rose significantly. Compliance cannot be assumed in the outpatient with a serum theophylline level in the therapeutic range or in the hospitalized patient. Determination of serum theophylline level after supervised drug administration is recommended in inpatients requiring unusually high doses of theophylline or in those whose condition is poorly controlled despite having serum theophylline levels in the therapeutic range (10 to 20 microgram/mL).

Adolescent↗

Thymic enlargement in association with hyperthyroidism.

T female adolescent with hyperthyroidism was found to have an anterior mediastinal mass. Radiological investigation of this mass was consistent with thymic enlargement. Chest roentgenograms one year after treatment showed resolution of the mediastinal mass. A non-invasive investigational approach to such patients is suggested based on a review of the pathological literature.

Adolescent↗

Intraphagocytic protection of staphylococci from extracellular penicillin.

In a system in which unphagocytosed bacteria were removed by differential centrifugation after a 30-min phagocytosis period, staphylococci associated with rabbit polymorphonulcear (PMN) leukocytes were completely protected from the effects of benzyl penicillin 1 microgram/ml, but not completely protected from the effects of 5 micrograms/ml. When unphagocytosed bacteria were lysed with lysostaphin, effective protection could be observed over a range of penicillin concentrations from 0.25 to 200 micrograms/ml. 14C-benzyl penicillin failed to accumulate in rabbit PMN leukocytes, whether or not they had previously phagocytosed staphylococci, in conditions in which mouse peritoneal macrophages readily accumulated penicillin. Mixed granule extracts prepared from the PMN leukocytes interacted synergically with penicillin against staphylococci at physiological pH (7.2) but failed to show synergy at an intraphagolysosomal pH of 5.0 unless the bacteria were first sublethally treated with penicillin. Experiments in which the pH value of culture media was changed either from 7.2 to 5.0 or from 5.0 to 7.2 indicated that the partial nature of the protective effect of the intraphagolysosomal environment could be attributed to the growth-limiting effects of the low phagolysosomal pH, which prevents full expression of the synergic potential of granule contents and penicillin. The concentration-dependent nature of the protection and its incompleteness are explained by supposing that a proportion of the staphylococci not ingested during the 30-min phagocytosis period are modified by penicillin in a way that opsonises them and potentiates the intrinsic bactericidal mechanisms of the PMN leukocytes when the bacteria are subsequently ingested.

Animals↗

An evaluation of the initial treatment of acute asthma.

Two treatment regimens for the initial treatment of acute asthma in 50 patients between the ages of 12 and 20 years seen in the emergency room were evaluated. The treatments were randomized such that 26 patients received 2.5 mg of the beta 2-agonist fenoterol by nebulizer and 24 patients received 0.3 mg of epinephrine followed by 0.75 mg of Sus-Phrine. Clinical assessment and spirometry were performed over a two-hour period. Both groups responded within ten minutes and peak improvement was reached within one hour. Peak expiratory flow and clinical score were better following fenoterol treatment in the first hour (P less than .05). The one-second forced expiratory volume and the forced expiratory flow in the middle half of the vital capacity were greater at 20 minutes with fenoterol (P less than .05). Those with more severe obstruction (forced expiratory volume less than 30%) receiving aerosol therapy also had significantly greater improvement in the first 20 minutes compared with those who received injections. Four patients failed to respond to epinephrine whereas all patients showed improvement with fenoterol (P less than .05). These results demonstrated that an inhaled beta 2-agonist is effective in the initial treatment of acute asthma in children, regardless of severity, and avoids the need for injections.

Acute Disease↗

A prospective study of group B streptococcal colonization in parturient mothers and their infants.

The objective of this study was to investigate the rates of group B streptococcal colonization among parturients within the 24 hours prior to delivery and colonization of their newborns. It was also to identify high risk factors. 204 parturients were randomly selected in the Alexandra Hospital, Singapore. Swabs for culture were taken from the maternal vagina and throat and the neonate's ears, throat and umbilicus. In this study it was found that vaginal colonization in the mother is significantly associated with neonatal colonization. Among the various ethnic groups, Malays and Indians/Pakistanis are at a higher risk of having vaginal colonization. All other factors studied, however, failed to show any influence on neonatal colonization and thus appear to have had no forewarning value.

Adult↗

Selective depression of 2,4-dinitrophenol depolarized canine Purkinje fibers by lidocaine.

Concentrations of lidocaine which minimally decrease conduction and excitability of normal canine Purkinje fibers markedly decrease these parameters in fibers depolarized by metabolic depression (DNP superfusion). The decrease in Vmax and the slowing of the post-stimulation recovery of Vmax by lidocaine are also more marked during DNP superfusion than during superfusion with a DNP-free salt solution. Since these effects could be reversed by a lidocaine-free DNP superfusion, it is concluded that lidocaine selectivity depresses the electrical activity of tissue depolarized by the metabolic inhibitor DNP. This selective depressive action of lidocaine is similar to that observed in cardiac tissues depolarized by other means.

Action Potentials↗

Structural analysis of the dur loci in S. cerevisiae: two domains of a single multifunctional gene.

In Saccharomyces cerevisiae, the degradation of urea to carbon dioxide and ammonia is catalyzed by urea carboxylase and allophanate hydrolase. The loci coding for these enzymes (dur1 and dur2) are very tightly linked on the right arm of chromosome II between pet11 and met8. Pleiotropic mutations that fail to complement mutations in either of the dur loci were found to be predominantly located in or near the dur2 locus. We interpret these data as suggesting that the two dur loci might in reality be domains of a single gene that codes for a multifunctional polypeptide. In view of this conclusion, we have renamed the dur loci as the dur1,2 locus.

Allophanate Hydrolase↗

Phagocytosis measured as inhibition of uridine uptake: a method that distinguishes between surface adherence and ingestion.

Polymorphonuclear leucocytes selectively inhibited the incorporation of 14C-uridine by intracellular staphylococci. Within specified limits, the amount of radiolabel incorporated by extracellular staphylococci was related to bacterial concentration. The incorporation of labelled uridine can thus be exploited to assay the extent to which association between staphylococci and polymorphonuclear leucocytes reflects surface adherence as opposed to ingestion. A comparison of the new method with a conventional viable-count determination of leucocyte-associated bacteria shows it to be comparable in efficiency when non-immune serum is used as opsonin and superior when specific opsonin is used.

Cell Membrane↗