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Biomedical subjects

H Lam

Publications and source records attributed to H Lam.

At least 19 recordsLinked to original sources
PubMed2006

HSV-1-mediated NGF delivery delays nociceptive deficits in a genetic model of diabetic neuropathy.

A previous phase III clinical trial failed to show significant therapeutic benefit of repeated subcutaneous nerve growth factor (NGF) administration in the treatment of diabetic neuropathy. Animal studies have since shown that site-specific viral-mediated expression of NGF in the lumbar dorsal root ganglia prevents peripheral nerve dysfunction associated with chemically induced neuropathy. Using a Herpes simplex virus expression vector, we have investigated the effect of localized NGF expression in a genetic mouse model of progressive diabetic neuropathy, the +/+ Leprdb mouse. We found that site-specific delivery of NGF initially delayed the appearance of hypoalgesia, assessed by the Hargreaves test, by 1 month and effectively attenuated this deficit for 2 months over the approximately 10 months normal life-span of these animals. Once the disease progressed into its more severe stages, NGF, although still capable of altering the electrophysiological profile of the sensory A- and C-fibers and influencing the expression of p75 and substance P in the dorsal root ganglia, could no longer maintain normal nociception. These data suggest that maximal therapeutic benefit in future NGF-based gene therapy trials will be gained from early applications of such viral-mediated neurotrophin delivery.

Action Potentials↗
PubMed2006

A new recombinant mosquito salivary allergen, rAed a 2: allergenicity, clinical relevance, and cross-reactivity.

BACKGROUND: Mosquito salivary proteins cause allergic reactions in humans. The allergenicity, clinical relevance, and species cross-reactivity of a new 37-kDa recombinant mosquito (Aedes aegypti) salivary allergen, rAed a 2, were evaluated. METHODS: rAed a 2 was expressed using a baculovirus/insect cell system and purified. Its allergenicity was examined using an enzyme-linked immunosorbent assay (ELISA), ELISA inhibition tests, immunoblots, and skin tests. Epicutaneous tests with the allergen, mosquito whole body extracts, and mosquito bite tests were performed on 48 volunteers. Serum rAed a 2-specific immunoglobulin E (IgE) was measured in individuals with positive mosquito saliva-specific IgE and negative controls. RESULTS: Both immunoblots and ELISAs demonstrated that rAed a 2 bound to the IgE of mosquito-allergic individuals. The binding could be inhibited by the addition of a natural mosquito preparation. Furthermore, rAed a 2 induced immediate and delayed skin reactions. Ten per cent of 31 participants with a positive mosquito bite test had positive skin reactions to rAed a 2, compared with 32% for mosquito whole body extract. None of the participants with a negative bite test showed positive reactions to either of the two extracts. Forty-three per cent of individuals with positive saliva-IgE had positive rAed a 2-IgE. rAed a 2 was a species-shared allergen, being present in the saliva of the 11 species studied. CONCLUSIONS: rAed a 2 has identical antigenicity and biologic activity to its native form. It can be used in the diagnosis of mosquito allergy, and is an important species-shared antigen.

Adult↗
PubMed2005

Relationship between cerebroplacental Doppler ratio and birth weight in postdates pregnancies.

OBJECTIVES: To explore the relationship between cerebroplacental Doppler impedance index and birth weight in postdates pregnancies, and to evaluate the use of a combination of Doppler parameters and ultrasound biometry in the prediction of large-for-gestational age (LGA) fetuses at 41 weeks of gestation. METHODS: The pulsatility indices of the umbilical (UA-PI) and middle cerebral (MCA-PI) arteries, the cerebroplacental pulsatility index ratio (CPR) and the estimated fetal weight (EFW) were obtained in a cohort of 181 ultrasound-dated pregnancies at 41 weeks' gestation, 2 days before induction of delivery. A regression equation was established and the correlation between umbilical artery impedance and different birth-weight centile groups was determined. A receiver-operating characteristics (ROC) curve was used to compare prediction of LGA fetuses using biometry alone with that using biometry and UA-PI. RESULTS: UA-PI was inversely related to EFW (Spearson's correlation coefficient rho = -0.28, P < 0.001). Logistic regression showed an independent contribution of UA-PI to the birth-weight estimation (birth weight = 1356.8 - 232.0 x UA-PI + 0.65 x EFW). On ROC curve analysis, the prediction of LGA with the regression equation was comparable to that using ultrasound biometry alone. CONCLUSION: UA-PI was inversely correlated to EFW, but the combination of ultrasound biometry and UA-PI compared with biometry alone showed similar prediction of LGA fetuses in postdates pregnancies. Further prospective trials on larger populations or groups with a higher prevalence of LGA fetuses would be needed to validate the use of the new formula.

Adult↗
PubMed2005

The use of fetal Doppler cerebroplacental blood flow and amniotic fluid volume measurement in the surveillance of postdated pregnancies.

BACKGROUND: This prospective observational study aims at determining the distribution of fetal cerebro-placental Doppler indices and amniotic fluid volume in a homogenous group of uncomplicated postdated pregnancies at 41 weeks. The correlation with incidence of passage of thick meconium-stained liquor in labor was analyzed to decide which parameter would be useful in the surveillance of postdated pregnancies. METHODS: The amniotic fluid volume, middle cerebral artery pulsatility index, umbilical artery pulsatility index, and cerebroplacental ratio were measured and distribution determined in 118 well-dated singleton pregnancies admitted for routine induction of labor at 41 weeks. The 10th centile and the 90th centile in each Doppler parameter and amniotic fluid volume were chosen to divide each parameter into three centile groups. The prevalence of thick meconium-stained liquor in labor in different Doppler and amniotic fluid volume centile groups was compared using Chi-square test for trend with P < 0.05 taken as statistically significant. RESULTS: The prevalence of thick meconium-stained liquor in labor was significantly inversely correlated with the middle cerebral artery pulsatility index (P = 0.008), with significant difference across different middle cerebral artery pulsatility index centile groups (P = 0.02). There was no significant difference in the prevalence of thick meconium-stained liquor in labor or oligohydramnios across different umbilical artery pulsatility index centile groups. Neither was there significant difference in the prevalence of thick meconium-stained liquor in labor and oligohydramnios across different cerebroplacental ratio and amniotic fluid volume centile groups. Logistic regression using the 10th centile of middle cerebral artery pulsatility index confirmed that it was a significant independent predicting factor for risk of thick meconium-stained liquor in labor with adjusted odds ratio (95th CI) of 6.14 (1.6-24.1). CONCLUSION: Middle cerebral artery pulsatility index is better than amniotic fluid volume or umbilical artery pulsatility index in predicting the risk of thick meconium-stained liquor in labor in uncomplicated postdated pregnancy at 41 weeks.

Adult↗
PubMed2005

Identification of a recurrent mutation in the human hairless gene underlying atrichia with papular lesions.

Identification of mutations in the hairless (HR) gene in patients with atrichia with papular lesions (APL) has proven of critical importance, as it provides a basis for the differentiation between APL and alopecia universalis. The establishment of the diagnostic criteria for APL has triggered the identification of a large number of APL patients among those suspected to suffer from alopecia universalis. This advancement has resulted in the discovery of an increasing number of hairless mutations in both consanguineous and nonconsanguineous APL families. Here, we report the identification of a homozygous mutation, 3434delC, in an APL patient of Arab-Palestinian descent. The proband is a 23-year-old female with generalized scalp and body alopecia. To confirm the diagnosis of APL and to identify the specific mutation, we sequenced the hairless gene. Sequencing of all exons of the hairless gene revealed a homozygous frameshift mutation, 3434delC, in exon 18. Interestingly, the same mutation was previously identified in an Arab-Israeli family. Our data suggest that the 3434delC mutation most likely represents a founder mutation in this geographical region.

Adult↗
PubMed2004

A comparison of hepatitis C treatment and outcomes at academic, private and Veterans' Affairs treatment centres.

BACKGROUND: Currently, there is a lack of published data examining hepatitis C treatment practices in different care settings. AIM: To provide data describing treatment practices for patients with hepatitis C virus infection in actual clinical practice, and to examine clinical outcomes in patients treated with interferon alpha-2b/ribavirin combination therapy in academically affiliated centres, private treatment centres and Veterans' Affairs treatment centres. METHODS: This multi-centre, retrospective, cohort study of 231 patients examined hepatitis C virus treatment practices in patients receiving interferon alpha-2b from January 1997 to May 2001 and explored outcomes in academically affiliated, private and Veterans' Affairs centres. RESULTS: Differences in treatment practice and use of diagnostic procedures were found. Genotype testing was under-utilized in non-academic sites (academic centres, 79.2%; private centres, 33.7%; Veterans' Affairs centres, 35.9%; P<0.001). Liver biopsies were performed less often in private sites (academic centres, 95.8%; private centres, 80.0%; Veterans' Affairs centres, 92.2%; P<0.01). End-of-treatment viral response (academic centres, 40.0%; private centres, 31.3%; Veterans' Affairs centres, 17.2%; P<0.05) was lower than that found in published trial data. Multivariate analysis revealed genotype 1 as the single significant predictor of treatment failure (P<0.01). CONCLUSIONS: Outside of the academic setting, there is significantly less diagnostic work-up performed prior to the initiation of hepatitis C virus therapy. This suggests a need for a standardization of care across treatment settings.

Academic Medical Centers↗
PubMed2004

Doppler study of the umbilical and fetal middle cerebral arteries in women with gestational diabetes mellitus.

OBJECTIVE: To investigate the correlation between Doppler parameters in the umbilical and fetal middle cerebral arteries and pregnancy outcome in women with gestational diabetes mellitus (GDM). METHODS: A prospective study was performed on 169 singleton GDM pregnancies in a university teaching hospital from January to December 2002. Umbilical artery (UA) pulsatility index (PI) and middle cerebral artery (MCA) PI and peak systolic velocity (Vmax) were measured every 4 weeks until delivery from the time of diagnosis of GDM. The pregnancy outcome was obtained from the hospital database. Using linear or quadratic regression, lines of best fit were drawn to compare the Doppler measurements between the two groups with normal and abnormal pregnancy outcomes. RESULTS: One hundred and thirty-eight women with known pregnancy outcome completed the study. A total of 305 Doppler examinations were performed with one to four examinations for each woman. Thirty-eight women (27.5%) had one or more abnormal pregnancy outcomes: placental abruption, pre-eclampsia, preterm delivery, small-for-gestational age (SGA) infants, low Apgar scores, neonatal jaundice requiring treatment, sepsis, birth trauma, meconium aspiration syndrome, respiratory and neurological complications. There was extensive overlap of the UA-PI, MCA-PI and MCA-Vmax measurements between the two groups. CONCLUSION: A Doppler study of the UA-PI, MCA-PI and MCA-Vmax was not useful in the prediction of abnormal pregnancy outcome in GDM.

Blood Flow Velocity↗
PubMed2004

Endogenous opioids mediate basal hedonic tone independent of dopamine D-1 or D-2 receptor activation.

Exogenously administered opiates are recognized as rewarding and the involvement of dopamine systems in mediating their apparent pleasurable effects is contentious. The aversive response to naloxone administration observed in animal studies suggests the presence of an endogenous opioid tone regulating hedonic state. We sought evidence for the requirement for dopamine systems in mediating this action of endogenous opioids by determining whether mice deficient in dopamine D-1 or D-2 receptors were able to display conditioned place aversion to naloxone. Mice received saline in the morning in one chamber and either saline or naloxone (10 mg/kg, s.c.) in the afternoon in another chamber, each day for 3 days. On the test day they were given free access to the testing chambers in the afternoon. Similar to their wild-type littermates, D-1 and D-2 receptor knockout mice receiving naloxone in the afternoon spent significantly less time on the test day in the compartment in which they previously received naloxone, compared with animals receiving saline in the afternoon. The persistence of naloxone-conditioned place aversion in D-1 and D-2 knockout mice suggests that endogenous opioid peptides maintain a basal level of positive affect that is not dependent on downstream activation of dopamine systems involving D-1 or D-2 receptors.

Affect↗
PubMed2004

A pilot-randomized comparison of sublingual misoprostol with syntometrine on the blood loss in third stage of labor.

BACKGROUND: To compare sublingual misoprostol with intravenous syntometrine use during third stage of labor by measuring the blood loss. METHODS: Sixty women were randomized to receive either 600 micro g misoprostol sublingually or 1 ml syntometrine intravenously during the third stage of labor after spontaneous vaginal delivery. For those with risk factors of postpartum hemorrhage such as medical induction or augmentation of labor, previous third stage complications were excluded. The blood loss in labor was measured by the alkaline-hematin method, and differences in hemoglobin before and after delivery were compared. RESULTS: There was no significant difference in the median measured blood loss between the misoprostol group and the syntometrine group (280 versus 226 ml, p = 0.45). The change in hemoglobin was comparable between the two groups. There were more women in the misoprostol group who required additional oxytocics, but the difference was not statistically significant. A major complication occurred in one patient in the misoprostol group with blood loss in excess of 1000 ml. The incidence of side effects such as shivering and pyrexia in women receiving misoprostol was significantly higher than that in the syntometrine group. CONCLUSION: The use of sublingual misoprostol or intravenous syntometrine in spontaneous vaginal delivery resulted in a comparable amount of blood loss. Transient side effect such as fever and shivering which resolved within a day occurred more frequent to those who received sublingual misoprostol.

Administration, Sublingual↗
PubMed2003

Successful early in utero management of fetal hydrothorax in a twin pregnancy.

We present a case of dichorionic diamniotic twin pregnancy in which one of the fetuses was found to have a major pleural effusion at 15 weeks of gestation. A single-needle pleural fluid aspiration was performed at 15 and 16 weeks, but the fluid reaccumulated quickly after each procedure and at 16 weeks, the fetus was found to become progressively hydropic. A shunt was then successfully inserted at 17 weeks, which is the earliest gestation reported so far in the literature for such a procedure to treat isolated hydrothorax. Because we felt that the fetus would be too small for a classical double-pigtail pleuroamniotic shunt, we used a multilength double-pigtail bladder stent (Harrison drain; Cook; Spencer; Indiana; USA) via a 13-gauge echo tip trocar. This shunt could be used for both singleton and twin pregnancies presenting with fetal pleural effusion from as early as 16 to 17 weeks to prevent the development of fetal hydrops and polyhydramnios and subsequent premature delivery. Treatment at this stage of gestation would also minimize the risk of lung hypoplasia, which is the main clinical issue when shunts are inserted after 24 weeks.

Amnion↗
PubMed2002

Thrombin-enhanced matrix metalloproteinase-1 expression: a mechanism linking placental abruption with premature rupture of the membranes.

OBJECTIVE: Given the strong clinical association between the decidual hemorrhage of placental abruption and subsequent preterm premature rupture of the membranes, we assessed the effects of thrombin on the expression of the potent interstitial collagenase, matrix metalloproteinase-1 (MMP-1), in cultured endometrial stromal and decidual cells. STUDY DESIGN: Stromal cells derived from predecidualized cycling endometrium and decidual cells from term decidua were cultured in a defined medium containing estradiol, to mimic the hormonal milieu of the non-pregnant proliferative phase, or estradiol plus medroxyprogesterone acetate (MPA), to mimic the hormonal milieu of pregnancy, in the presence and absence of thrombin. Culture media were examined for MMP-1 protein levels and cell lysates were examined for steady-state MMP-1 mRNA levels. RESULTS: MPA strongly inhibited MMP-1 levels in endometrial stromal and term decidual cells. However, thrombin overcame this suppression, producing MMP-1 levels that were several-fold higher than control levels. CONCLUSION: Extrapolation of thrombin-enhanced MMP-1 expression in cultured endometrial stromal and decidual cells to the in vivo pregnant state provides an explanation for the strong association between placental abruption and preterm membrane rupture.

Abruptio Placentae↗
PubMed2001

Characterization of neutralization epitopes of simian immunodeficiency virus (SIV) recognized by rhesus monoclonal antibodies derived from monkeys infected with an attenuated SIV strain.

A major limitation in the simian immunodeficiency virus (SIV) system has been the lack of reagents with which to identify the antigenic determinants that are responsible for eliciting neutralizing antibody responses in macaques infected with attenuated SIV. Most of our information on SIV neutralization determinants has come from studies with murine monoclonal antibodies (MAbs) produced in response to purified or recombinant SIV envelope proteins or intact SIV-infected cells for relatively short periods of time. While these studies provide some basic information on the potential immunogenic determinants of SIV envelope proteins, it is unclear whether these murine MAbs identify epitopes relevant to antibody responses elicited in monkeys during infection with either wild-type or attenuated SIV strains. To accomplish maximum biological relevance, we developed a reliable method for the production of rhesus monoclonal antibodies. In the present study, we report on the production and characterization of a unique panel of monoclonal antibodies derived from four individual monkeys inoculated with SIV/17E-CL as an attenuated virus strain at a time when protective immunity from pathogenic challenge was evident. Results from these studies identified at least nine binding domains on the surface envelope glycoprotein; these included linear determinants in the V1, V2, cysteine loop (analogous to the V3 loop in human immunodeficiency virus type 1), and C5 regions, as well as conformational epitopes represented by antibodies that bind the C-terminal half of gp120 and those sensitive to defined mutations in the V4 region. More importantly, three groups of antibodies that recognize closely related, conformational epitopes exhibited potent neutralizing activity against the vaccine strain. Identification of the epitopes recognized by these neutralizing antibodies will provide insight into the antigenic determinants responsible for eliciting neutralizing antibodies in vivo that can be used in the design of effective vaccine strategies.

Amino Acid Sequence↗
PubMed2001

Genetic dissection of the Streptococcus pyogenes M1 protein: regions involved in fibronectin binding and intracellular invasion.

Entry of serotype M1 Streptococcus pyogenes into host cells depends on binding of the host glycoprotein fibronectin (Fn) by the bacterial M1 protein. The present study was undertaken to localize the Fn binding region in M1 and assess other potential functions of M1. A set of recombinant M1 protein fragments were assayed for their capacities to bind Fn and inhibit ingestion of streptococci by epithelial cells. M1 protein, M6 protein and internally-deleted derivatives of M1 were expressed on the surface of Lactococcus lactis. Lactococci that expressed M1 or M6 protein bound Fn and were efficiently taken up by epithelial cells. Deletion of both the N-terminal A and B repeats regions of M1 abrogated Fn binding and intracellular invasion. Deletion of either the A domain (M1DeltaA) or B repeats (M1DeltaB) significantly reduced, but did not completely eliminate, Fn binding indicating that M1 protein may possess two independent Fn binding sites. Fn binding by the M1DeltaA or M1DeltaB proteins was insufficient for efficient invasion, however, suggesting that M protein binding alters the structure of Fn that, in turn, affects the interaction between Fn and epithelial cells. Although expression of M1, M6 or M1DeltaB proteins led to aggregation of lactococcal cells, aggregation did not significantly contribute to invasion efficiency.

Amino Acid Sequence↗
PubMed2001

Expression, purification, characterization and clinical relevance of rAed a 1--a 68-kDa recombinant mosquito Aedes aegypti salivary allergen.

Accurate diagnosis of mosquito allergy has been precluded by the difficulty of obtaining salivary allergens. In this study, we expressed, purified, characterized and investigated the clinical relevance of a recombinant Aedes aegypti salivary allergen, rAed a 1. Two cDNA segments were ligated together to form the full-length Aed a 1 gene. rAed a 1 was expressed using a baculovirus/insect cell system, and purified using a combination of anion-exchange and gel-filtration chromatography. The purified rAed a 1 bound to human IgE, as detected by ELISA, ELISA inhibition tests and immunoblot analyses. Epicutaneous tests with rAed a 1 and a commercial whole-body AE: aegypti extract, and AE: aegypti bite tests were performed in 48 subjects. Nine of 31 (29%) of the subjects with positive immediate bite tests also had a positive rAed a 1 immediate skin reaction and 32% had an positive immediate test to the commercial extract. Six of 33 (18%) of the subjects with positive delayed bite tests also had a positive rAed a 1 delayed skin reaction and 6% had a positive delayed test to the commercial extract. Furthermore, rAed a 1-induced flare sizes significantly correlated with mosquito bite-induced flare sizes. None of the subjects with negative bite tests had a positive skin test to rAed a 1 or to commercial extract. We conclude that the rAed a 1 has identical antigenicity and biological activity to native Aed a 1, can be used in the in vitro and in vivo diagnosis of mosquito allergy, and is more sensitive than mosquito whole-body extract for detecting delayed skin reactions.

Aedes↗
PubMed2001

Identification of a founder mutation in the protoporphyrinogen oxidase gene in variegate porphyria patients from chile.

Variegate porphyria (VP; OMIM 176200) is characterized by a partial defect in the activity of protoporphyrinogen oxidase (PPO), the seventh enzyme of the porphyrin-heme biosynthetic pathway. The disease is usually inherited as an autosomal dominant trait displaying incomplete penetrance. In an effort to characterize the spectrum of molecular defects in VP, we identified 3 distinct mutations in 6 VP families from Chile by PCR, heteroduplex analysis, automated sequencing, restriction enzyme digestion and haplotyping analysis. The mutations consisted of 2 deletions and 1 missense mutation, designated 1239delTACAC, 1330delT and R168H. The occurrence of the missense mutation R168H had been reported previously in American, German and Dutch VP families, suggesting that this may represent a frequent recurrent mutation. Interestingly, the mutation 1239delTACAC was found in patients from 4 unrelated families living in different parts of Chile, suggesting that it might represent a common mutation in Chile. Haplotype analysis using 15 microsatellite markers which closely flank the PPO gene on chromosome 1q22, spanning approximately 21 cM, revealed the presence of R168H on different haplotypes in 6 VP patients from 3 unrelated families. In contrast, we found the occurrence of 1239delTACAC on the same chromosome 1 haplotype in 11 mutation carriers from 4 unrelated families with VP. These findings are consistent with R168H representing a hotspot mutation and 1239delTACAC existing as a founder mutation in the PPO gene. Our data comprise the first genetic studies of the porphyrias in South America and will streamline the elucidation of the genetic defects in VP patients from Chile by allowing an initial screening for the founder mutation 1239delTACAC.

Chile↗
PubMed2000

Increases in serum concentrations of cardiac proteins and the prediction of early postoperative cardiovascular complications in noncardiac surgery patients.

We investigated the use of measurements of serum concentrations of the cardiac proteins troponins I and T as biochemical markers of myocardial cell damage in 80 patients undergoing vascular or major orthopaedic surgery. Holter electrocardiographic monitoring was carried out before surgery and for 3 days after surgery. Blood samples for troponins I and T and creatine kinase-MB isoenzyme were taken on each of these 4 days. Outcome was assessed at 3 months using a patient questionnaire, general practitioner follow-up and case notes review. Silent postoperative myocardial ischaemia was detected in 21 patients; increases in troponins I and T and creatine kinase-MB occurred in four, six and 17 of these patients, respectively. Eight patients suffered major postoperative complications (cardiac death, myocardial ischaemia, congestive cardiac failure, unstable angina and cerebrovascular accident) and 21 minor complications (poorly controlled hypertension needing increased or new additional treatment, palpitations, increased tiredness or shortness of breath in the absence of known respiratory disease). There were no associations between postoperative ischaemia and cardiac protein concentrations. The relative odds for the associations of major adverse outcome at 3 months after surgery and postoperative ischaemia or increased serum concentrations of the three proteins were 5.39 [95% confidence intervals 1.16-27.67] for postoperative ischaemia; 5.64 [1.07-31.00] for creatine kinase-MB isoenzyme; 17.00 [2.20-116.54] for troponin T and 13.20 [1.12-135.00] for troponin I. We found troponin T to be the only prospective marker for both major and minor cardiovascular complications (relative odds 10.65 [1.26-252.88]).

Aged↗
PubMed2000

Xanthogranulomatous tubo-ovarian abscess resulting from chronic diverticulitis.

We report a case of xanthogranulomatous tubo-ovarian abscess which was preoperatively suspected to be an adnexal neoplasm. With foreign body material found in the abscess wall and vegetable fiber in the tubal lumen, a previously treated chronic diverticulitis was the presumed cause. Culture studies showed polymicrobial isolates which included Escherichia coli, an enteric pathogen. After surgery, administration of antibiotics, and revision of delayed subcutaneous wound healing, the patient is reportedly well.

Abscess↗