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G M Shaw

Publications and source records attributed to G M Shaw.

At least 109 records · Page 6Linked to original sources
PubMed1996

Parental recreational drug use and risk for neural tube defects.

The authors investigated whether maternal or paternal periconceptional use of recreational drugs increased the risk of having neural tube defect (NTD)-affected pregnancies using a population-based case-control study of fetuses and liveborn infants with NTDs among 1989-1991 California births. Face-to-face interviews were conducted with mothers of 538 (88% of eligible) NTD cases and 539 (88%) nonmalformed controls, usually within 5 months of delivery. Periconceptional maternal use of cocaine (odds ratio (OR) = 0.74, 95% confidence interval (CI) 0.40-1.4), amphetamines/speed (OR = 0.68, 95% CI 0.39-1.2), or marijuana (OR = 0.64, 95% CI 0.43-0.95) or preconceptional use of alcohol as < 1 drink/day (OR = 0.80, 95% CI 0.62-1.0) or > or = 1 drink/day (OR = 0.69, 95% CI 0.42-1.2) or of cigarettes as < 1 pack/day (OR = 0.90, 95% CI 0.65-1.2) or > or = 1 pack/day (OR = 0.59, 95% CI 0.36-0.96) did not increase the risk for delivering NTD-affected offspring. Risks were not substantially altered after adjustment for maternal age, race/ethnicity, vitamin use, education, and household income. Increased NTD risk was also not generally associated with paternal drug use. The authors could not discern whether the decreased risks observed for these maternal exposures reflected a true association or were due to reporting bias, a disproportionate number of drug-exposed NTD cases among spontaneous abortuses that could not be ascertained, or some other bias.

Case-Control Studies↗
PubMed1996

Impact of prenatal diagnosis and elective termination on prevalence and risk estimates of neural tube defects in California, 1989-1991.

The authors examined the impact of prenatal diagnosis and elective termination of neural tube defect (NTD)-affected pregnancies on NTD prevalence and risk estimates. Prevalence data were actively ascertained and were derived from a population-based 1989-1991 cohort of California births. Included were 664 singleton infants/fetuses with an NTD. The birth prevalence (livebirths and stillbirths only) was 48.4% of the total prevalence (including elective terminations) for anencephaly and 70.2% for spina bifida. The authors also used in-person interview data from mothers of 538 of the ascertained NTD cases and mothers of 539 randomly selected nonmalformed control infants to examine maternal/infant characteristics. Compared with women who delivered liveborn/stillborn infants with an NTD, women who electively terminated NTD-affected pregnancies were disproportionately white, were more highly educated, had higher incomes, and used vitamins containing folic acid more often. For factors associated with elective terminations, risk estimates appeared biased when only liveborn and stillborn infants were included among cases compared with analyses in which all clinically recognized NTD-affected pregnancies were included.

Abortion, Legal↗
PubMed1996

Holoprosencephaly: epidemiologic and clinical characteristics of a California population.

Holoprosencephaly is a brain defect resulting from incomplete cleavage of the embryonic forebrain. It involves forebrain and facial malformations that can range from mild to severe. The epidemiology of holoprosencephaly is largely unknown. Published prevalence estimates have been derived from clinic-based case series, and suggested risk factors for holoprosencephaly have been identified in case reports, without confirmation from systematically conducted population-based studies. Using data from a population-based birth defects registry in California, we describe the epidemiologic and clinical characteristics of cytogenetically and phenotypically distinct types of holoprosencephaly. A total of 121 cases was identified among a cohort of 1,035,386 live births and fetal deaths. The prevalence of holoprosencephaly was 1.2 per 10,000 births (95% confidence interval 1.0-1.4 per 10,000). Of all cases, 41% (50/121) had a chromosomal abnormality, most commonly Trisomy 13. Among the 71 cytogenetically apparently normal cases, 18 had recognizable syndromes and the remaining 53 were of unknown cause. Among the cytogenetically abnormal cases, females had a greater risk than males (odds ratio = 2.3,95% confidence interval [1.2, 4.4]). Among the cytogenetically normal cases, increased risks were observed among Hispanic whites (OR = 1.8 [0.9, 3.6]) and cases whose mother was born in Mexico (OR = 2.2 [1.0, 4.5]). Approximately 46% of all cases had alobar holoprosencephaly, the most severe form of the forebrain malformation. The facial phenotype did not strongly predict the severity of the brain defect; however, severity was inversely correlated with length of survival. This study is the first to present findings based on such a large population-based series of infants/fetuses affected by holoprosencephaly, and demonstrates the importance of investigating the component subgroups of this rare phenotype.

Adult↗
PubMed1996

Kinetics of cytokine expression during primary human immunodeficiency virus type 1 infection.

In the present study, we have determined the kinetics of constitutive expression of a panel of cytokines [interleukin (IL) 2, IL-4, IL-6, IL-10, interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha)] in sequential peripheral blood mononuclear cell samples from nine individuals with primary human immunodeficiency virus infection. Expression of IL-2 and IL-4 was barely detected in peripheral blood mononuclear cells. However, substantial levels of IL-2 expression were found in mononuclear cells isolated from lymph node. Expression of IL-6 was detected in only three of nine patients, and IL-6 expression was observed when transition from the acute to the chronic phase had already occurred. Expression of IL-10 and TNF-alpha was consistently observed in all patients tested, and levels of both cytokines were either stable or progressively increased over time. Similar to IL-10 and TNF-alpha, IFN-gamma expression was detected in all patients; however, in five of nine patients, IFN-gamma expression peaked very early during primary infection. The early peak in IFN-gamma expression coincided with oligoclonal expansions of CD8+ T cells in five of six patients, and CD8+ T cells mostly accounted for the expression of this cytokine. These results indicate that high levels of expression of proinflammatory cytokines are associated with primary infection and that the cytokine response during this phase of infection is strongly influenced by oligoclonal expansions of CD8+ T cells.

Cells, Cultured↗
PubMed1996

Risk of neural tube defect-affected pregnancies among obese women.

OBJECTIVE: To investigate the risk for neural tube defect (NTD)-affected pregnancies among obese women (ie, women with a body mass index [BMI] > 29kg/m2) compared with women of average prepregnancy weight. DESIGN: Population-based case-control study. SETTING: All hospitals in 55 of 58 counties in California. PARTICIPANTS: In-person interviews were conducted with mothers of 538 (88% of eligible) NTD cases (including fetuses and infants electively terminated, stillborn, or born alive) and with mothers of 539 nonmalformed controls (88%) within an average of 5 months from the term delivery date. MAIN OUTCOME MEASURES: The risk of an NTD-affected pregnancy among obese women. RESULTS: Compared with women whose BMI was less than or equal to 29 kg/m2, an increased risk for NTD-affected pregnancy was observed among obese women (odds ratio, 1.9; 95% confidence interval, 1.3 to 2.9). The increased risk was not attributable to maternal nonuse of a vitamin containing folic acid, diabetes, use of diet pills, lower dietary folate intake, or an NTD-pregnancy history. Adjustment for maternal age, education, gravidity, use of vitamins, and use of alcohol did not change the odds ratio. The risk associated with maternal obesity was greater for spina bifida and for other less prevalent NTDs than for anencephaly. CONCLUSION: Because as many as 10% of women may be obese periconceptionally, the observed twofold increased risk is relevant to the population burden of NTDs.

Adult↗
PubMed1996

Chorionic villus sampling and transverse digital deficiencies: evidence for anatomic and gestational-age specificity of the digital deficiencies in two studies.

Several but not all studies indicate that chorionic villus sampling (CVS) is associated with an increased risk for transverse limb deficiencies, including digital deficiencies. It has been suggested that variations in results regarding the transverse digital deficiencies (TDDs) may be due to the use of different classification criteria. We present the combined analysis of two case-control studies, the U.S. Multistate CVS (US) study and the Italian Multicentric Birth Defects (IP-IMC) study, using two different definitions of TDDs. We compared the frequency of CVS exposure in control infants with that among those infants with any number of affected digits (any TDD), and those with all five digits of at least one limb affected (extensive TDDs). The estimated relative risk (RR) for any TDD following CVS was 10.6 (IPIMC) and 6.6 (US). For the extensive TDDs, the RR was 30.5 (IPIMC) and 10.7 (US). In both studies, extensive TDDs were less than 25% of all TDDs. Compared to all TDDs, extensive TDDs were more likely to occur after CVS performed earlier in the first trimester (before 10-11 weeks' gestation). These findings suggest a relationship between the timing of CVS and the severity of TDDs; indicate that using a restrictive definition of TDDs (all five digits affected) may limit the ability to evaluate the association between CVS and TDDs in populations in whom CVS is usually performed at or after 10 weeks' gestation; and highlight the necessity to consider gestational age in any evaluation of the relative risk for limb deficiencies associated with CVS.

Adult↗
PubMed1996

Genetic variants of human T-lymphotrophic virus type II in American Indian groups.

The human T-lymphotropic virus type II (HTLV-II) is found in many New World Indian groups in North and South America and may have entered the New World from Asia with the earliest migration of ancestral Amerindians over 15,000 years ago. To characterize the phylogenetic relationships of HTLV-II strains infecting geographically diverse Indian populations, we used polymerase chain reaction to amplify HTLV-II sequences from lymphocytes of seropositive Amerindians from Brazil (Kraho, Kayapo, and Kaxuyana), Panama (Guaymi), and the United States (the Navajo and Pueblo tribes of the southwestern states and the Seminoles of Florida). Sequence analysis of a 780-base pair fragment (located between the env gene and the second exons of tax/rex) revealed that Amerindian viruses clustered in the same two genetic subtypes (IIa and IIb) previously identified for viruses from intravenous drug users. Most infected North and Central American Indians had subtype IIb, while HTLV-II infected members of three remote Amazonian tribes clustered as a distinct group within subtype IIa. These findings suggest that the ancestral Amerindians migrating to the New World brought at least two genetic subtypes, IIa and IIb. Because HTLV-II strains from Amazonian Indians form a distinct group within subtype HTLV-IIa, these Brazilian tribes are unlikely to be the source of IIa viruses in North American drug users. Finally, the near identity of viral sequences from geographically diverse populations indicate that HTLV-II is a very ancient virus of man.

Amino Acid Sequence↗
PubMed1996

Does periconceptional multivitamin use reduce the risk of neural tube defects associated with other birth defects? data from two population-based case-control studies.

The role of periconceptional folic acid in the prevention of neural tube defects (NTDs) is well established. However, it is not clear whether a protective effect exists for the subset of nonsyndromic NTD with other "unrelated" major structural birth defects (NTD-multiples). This question is important to investigate because of shared pathogenetic mechanisms between NTD and other types of birth defects, and because of the epidemiologic differences that have been shown between NTD-multiples and NTD-singles. We analyzed data from two population-based case-control studies of NTDs, Atlanta 1968-1980, and California 1989-1991, to assess whether periconceptional multivitamin use reduces the risk of NTD-multiples. Maternal vitamin histories were assessed for 47 and 65 NTD-multiples cases and 3,029 and 539 control babies in Atlanta, and California, respectively. There was a substantial risk reduction associated with periconceptional multivitamin use (-3 to +3 months) for NTD-multiples (pooled odds ratio = 0.36, 95% C.I. 0.18-0.72) that persisted after adjustment for maternal race/ethnicity and education. Also, no specific types of NTDs or NTDs with specific defects explained the risk reduction with vitamin use. These data suggest that multivitamins reduce the risk of nonsyndromic NTD cases associated with other major birth defects. The implication of this finding for the role of vitamins in the prevention of non-NTD birth defects should be further explored.

Abnormalities, Multiple↗
PubMed1996

Parental cigarette smoking and risk for congenital anomalies of the heart, neural tube, or limb.

Risks for selected congenital anomalies from parental smoking were investigated in a case-control study in California. Mothers of 207 infants with conotruncal heart defects, 264 infants with neural tube defects, 178 infants with limb deficiencies, and 481 live born control infants delivered in 1987-1988 were interviewed by telephone. Modestly elevated risks were observed for conotruncal heart defects and limb deficiencies, associated primarily with both parents smoking. An odds ratio of 1.9 (95 percent confidence interval 1.2-3.1) was observed for conotruncal heart defects and an odds ratio of 1.7 (95% confidence interval 0.96-2.9) for limb deficiencies when both parents smoked compared to neither parent smoking. We did not observe increased risks associated with maternal smoking in the absence of paternal smoking, although an increased risk associated with paternal smoking in the absence of maternal smoking was observed for limb deficiencies in offspring. For conotruncal defects, the risks associated with parental smoking differed among race/ethnic groups. Parental smoking was not associated with increased risks for neural tube defects. Observed risks did not change substantially when adjusted for maternal vitamin use, alcohol use, and gravidity. Some heterogeneity in risk was observed for phenotypic case subgroups, but data were too sparse to draw firm inferences.

Case-Control Studies↗
PubMed1996

Epidemiologic characteristics of conotruncal heart defects in California, 1987-1988.

In this population-based case-control study, we explored the association of selected parental and infant characteristics from the birth certificates of children with conotruncal heart defects. We compared 252 cases to a random sample of 5,000 nonmalformed infants from a cohort of 341,839 California live births for 1987-1988. The prevalence of conotruncal defects was 0.732 per 1,000 total births. A decreased risk (OR = 0.55, 95% CI0.33-0.89) for delivering infants with conotruncal defects was found among mothers born in Mexico compared to mothers born in California. An increased risk was observed for Native American mothers compared to non-Hispanic whites (OR = 2.6, 95% CI 1.1-6.0). We also compared risks associated with the individual diagnoses that comprise the group of conotruncal defects. Only minor differences in risk estimates between the anatomic diagnoses were observed, lending support to the methodologic approach of using conotruncal defects as a single category of heart defects in etiologic investigations.

California↗
PubMed1996

HIV viral load markers in clinical practice.

Plasma HIV RNA determinations are an important prognostic marker of disease progression and, when used appropriately, provide a valuable tool for the management of individual patients. But what constitutes appropriate use?

Antiviral Agents↗
PubMed1996

The heterosexual human immunodeficiency virus type 1 epidemic in Thailand is caused by an intersubtype (A/E) recombinant of African origin.

Since 1989, human immunodeficiency virus type 1 (HIV-1) has spread explosively through the heterosexual population in Thailand. This epidemic is caused primarily by viruses classified as "subtype E", which, on the basis of limited sequence comparisons, appear to represent hybrids of subtypes A (gag) and E (env). However, the true evolutionary origins of "subtype E" viruses are still obscure since no complete genomes have been analyzed, and only one full-length subtype A sequence has been available for phylogenetic comparison. In this study, we determined full-length proviral sequences for "subtype E" viruses from Thailand (93TH253) and the Central African Republic (90CR402) and for a subtype A virus from Uganda (92UG037). We also sequenced the long terminal repeat (LTR) regions from 16 virus strains representing clades A, C, E, F, and G. Detailed phylogenetic analyses of these sequences indicated that "subtype E" viruses do indeed represent A/E recombinants with multiple points of crossover along their genomes. The extracellular portion of env, parts of vif and vpr, as well as most of the LTR are of subtype E origin, whereas the remainder of the genome is of subtype A origin. The possibility that the discordant phylogenetic positions of "subtype E" viruses in gag- and env-derived trees are the result of unusual rates or patterns of evolution was also considered but was ruled out on the basis of two lines of evidence: (i) phylogenetic trees constructed for synonymous and nonsynonymous substitutions yielded the same discordant branching orders for "subtype E" gag and env gene sequences, thus excluding selection-driven evolution, and (ii) multiple crossovers in the viral genome are most consistent with the copy choice model of recombination and have been observed in other documented examples of HIV-1 intersubtype recombination. Thai and CAR "subtype E" viruses exhibited the same pattern of A/E mosaicism, indicating that the recombination event occurred in Africa prior to the spread of virus to Asia. Finally, all "subtype E" viruses were found to contain a distinctive two-nucleotide bulge in their transactivation response (TAR) elements. This feature was present only in viruses which also contained a subtype A 5' pol region (i.e., subtype A viruses or A/D and A/E recombinants), raising the possibility of a functional linkage between the TAR region and the polymerase. The implications of epidemic spread of a recombinant HIV-1 strain to viral natural history and vaccine development are discussed.

Africa↗
PubMed1996

Molecular cloning and analysis of functional envelope genes from human immunodeficiency virus type 1 sequence subtypes A through G. The WHO and NIAID Networks for HIV Isolation and Characterization.

Present knowledge of human immunodeficiency virus type 1 (HIV-1) envelope immunobiology has been derived almost exclusively from analyses of subtype B viruses, yet such viruses represent only a minority of strains currently spreading worldwide. To generate a more representative panel of genetically diverse envelope genes, we PCR amplified, cloned, and sequenced complete gp160 coding regions of 35 primary (peripheral blood mononuclear cell-propagated) HIV-1 isolates collected at major epicenters of the current AIDS pandemic. Analysis of their deduced amino acid sequences revealed several important differences from prototypic subtype B strains, including changes in the number and distribution of cysteine residues, substantial length differences in hypervariable regions, and premature truncations in the gp41 domain. Moreover, transiently expressed glycoprotein precursor molecules varied considerably in both size and carbohydrate content. Phylogenetic analyses of full-length env sequences indicated that the panel included members of all major sequence subtypes of HIV-1 group M (clades A to G), as well as an intersubtype recombinant (F/B) from an infected individual in Brazil. In addition, all subtype E and three subtype G viruses initially classified on the basis of partial env sequences were found to cluster in subtype A in the 3' half of their gp41 coding region, suggesting that they are also recombinant. The biological activity of PCR-derived env genes was examined in a single-round virus infectivity assay. This analysis identified 20 clones, including 1 from each subtype (or recombinant), which expressed fully functional envelope glycoproteins. One of these, derived from a patient with rapid CD4 cell decline, contained an amino acid substitution in a highly conserved endocytosis signal (Y721C), as mediated virus entry with very poor efficiency, although they did not contain sequence changes predicted to alter protein function. These results indicate that the env genes of primary HIV-1 isolates collected worldwide can vary considerably in their genetic, phylogenetic, and biological properties. The panel of env constructs described here should prove valuable for future structure-function studies of naturally occurring envelope glycoproteins as well as AIDS vaccine development efforts targeted against a broader spectrum of viruses.

Amino Acid Sequence↗
PubMed1996

A pilot investigation of high-frequency audiometry in obscure auditory dysfunction (OAD) patients.

The diagnosis of obscure auditory dysfunction (OAD) has been an elusive one, based primarily upon reports of poor speech perception in noise by the patient. Basic audiometric testing reveals hearing within normal threshold limits and it is thought that there may, in part be some subtle psychoacoustic and/or central auditory deficits causing this phenomenon. The use of high-frequency audiometry (HFA) as a test of subclinical cochlear damage has been well documented, especially to monitor the early effects of noise exposure and ototoxic drugs. However, it has not been used in the diagnosis of OAD patients. This study examines the use of HFA as an aid to the understanding of OAD pathophysiology. HFA was conducted on nine OAD subjects, each matched to two controls. Results indicate an elevated threshold amongst all frequencies (10-20 kHz) in OAD patients with significant differences occurring at 10, 14, 16 and 20 kHz. It could be postulated that OAD in fact, is the product of an ultra-high-frequency hearing impairment and its psychoacoustic sequelae. Furthermore, HFA may be a useful inclusion in a diagnostic test battery for OAD status. However, the degree to which it can be used may be limited due to the large intersubject variability in HFA thresholds in the normal population. It is suggested that further investigations into the ultra-high-frequency hearing abilities of OAD patients should be completed in the future.

Adolescent↗
PubMed1996

Orofacial clefts, parental cigarette smoking, and transforming growth factor-alpha gene variants.

Results of studies to determine whether women who smoke during early pregnancy are at increased risk of delivering infants with orofacial clefts have been mixed, and recently a gene-environment interaction between maternal smoking, transforming growth factor-alpha (TGFa), and clefting has been reported. Using a large population-based case-control study, we investigated whether parental periconceptional cigarette smoking was associated with an increased risk for having offspring with orofacial clefts. We also investigated the influence of genetic variation of the TGFa locus on the relation between smoking and clefting. Parental smoking information was obtained from telephone interviews with mothers of 731 (84.7% of eligible) orofacial cleft case infants and with mothers of 734 (78.2%) nonmalformed control infants. DNA was obtained from newborn screening blood spots and genotyped for the allelic variants of TGFa. We found that risks associated with maternal smoking were most elevated for isolated cleft lip with or without cleft palate, (odds ratio 2.1 [95% confidence interval 1.3-3.6]) and for isolated cleft palate (odds ratio 2.2 [1.1-4.5]) when mothers smoked > or =20 cigarettes/d. Analyses controlling for the potential influence of other variables did not reveal substantially different results. Clefting risks were even greater for infants with the TGFa allele previously associated with clefting whose mothers smoked > or =20 cigarettes/d. These risks for white infants ranged from 3-fold to 11-fold across phenotypic groups. Paternal smoking was not associated with clefting among the offspring of nonsmoking mothers, and passive smoke exposures were associated with at most slightly increased risks. This study offers evidence that the risk for orofacial clefting in infants may be influenced by maternal smoke exposures alone as well as in combination (gene-environment interaction) with the presence of the uncommon TGFa allele.

Adult↗
PubMed1995

Maternal periconceptional use of multivitamins and reduced risk for conotruncal heart defects and limb deficiencies among offspring.

We investigated whether a woman's periconceptional use of a multivitamin containing folic acid was associated with a reduced risk for delivering offspring with a conotruncal heart defect or a limb deficiency. Data were derived from a population-based case-control study of fetuses and liveborn infants with conotruncal or limb defects among a 1987-88 cohort of births in California. Telephone interviews were conducted with mothers of 207 (87.0% of eligible) conotruncal cases, 178 (82.0%) limb defect cases, and of 481 (76.2%) randomly selected liveborn nonmalformed control infants. Reduced risks were observed for maternal use of multivitamins containing folic acid from one month before until two months after conception. Odds ratios and 95% confidence intervals for any compared to no multivitamin use were 0.70 (0.46-1.1) for conotruncal defects and 0.64 (0.41-1.0) for limb defects. Controlling for maternal race/ethnicity, age, education, gravidity, alcohol use, and cigarette use resulted in a further reduction to the odds ratio for conotruncal defects, 0.53 (0.34-0.85), but not for limb defects. Among non-vitamin using women, consumption of cereal containing folic acid was also associated with reduced risk for both defects. Women who take multivitamins have 30-35% lower risk of delivering offspring with either conotruncal or limb defects. This association may not be attributable to folic acid specifically, but may be a consequence of other multivitamin components, or some unknown behaviors that highly correlate with regular use of a multivitamin. However, should the association prove causal, it offers an important opportunity for preventing thousands of serious birth defects.

Case-Control Studies↗
PubMed1995

Assessment of antiretroviral therapy by plasma viral load testing: standard and ICD HIV-1 p24 antigen and viral RNA (QC-PCR) assays compared.

To assess the utility of quantitative competitive-polymerase chain reaction (QC-PCR) measurements of plasma human immunodeficiency virus type 1 (HIV-1) RNA and other viral load markers for assessment of antiretroviral therapy, we used archived cryopreserved specimens from a randomized controlled clinical trial of 135 patients (CD4+ T cell count < or = 500/mm3), comparing zidovudine (500 mg/day) versus the nonnucleoside reverse transcriptase inhibitor L-697, 661 (50, 300, or 1,000 mg daily). We evaluated treatment-associated changes in plasma viral load by standard and immune complex-dissociated (ICD) HIV-1 p24 antigen assays, and, in a representative subset of patients (n = 46), by QC-PCR determination of virion-associated HIV-1 RNA. At baseline, HIV-1 RNA was quantifiable by QC-PCR in all patients tested (100%), whereas standard and ICD HIV-1 p24 antigen tests were positive (> or = 30 pg/ml) in 42% and 56%, respectively. All viral load parameters showed significant decreases from baseline within 1 week of initiation of zidovudine, as measured by standard p24 antigen assay, ICD p24 assay, and QC-PCR. At 1 week, patients treated with either 300 or 1,000 mg/day of L-697,661 showed significant decreases from baseline in plasma standard and ICD p24 antigen and QC-PCR-determined HIV-1 RNA levels. Whereas viral load decreases seen with zidovudine were sustained for the duration of treatment, plasma viral markers often returned to pretreatment levels despite ongoing L-697,661 treatment, with evidence of the emergence of drug-resistant virus. Whereas standard p24, ICD p24, and viral RNA levels changed similarly in response to treatment, the superior sensitivity and available dynamic range of plasma viral RNA assays like QC-PCR analysis provide an advantage for clinical monitoring of plasma viral load, allowing tracking of treatment-related changes even in patients with earlier stage disease and lower levels of viral load.

Antiviral Agents↗