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Biomedical subjects

C M Nolan

Publications and source records attributed to C M Nolan.

At least 19 recordsLinked to original sources
PubMed2004

Cultural case management of latent tuberculosis infection.

SETTING: The proportion of tuberculosis (TB) among foreign-born individuals in the United States is steadily increasing. Treatment of latent TB infection can prevent future cases of disease, although generally only 60% of patients who start a 6-month regimen of isoniazid complete therapy. OBJECTIVE: Cultural case management--employing case manager cultural mediators who serve patient-defined needs in addition to performing TB control functions--may improve results of testing and treatment in one high-risk group, new refugees. DESIGN: A cultural case management approach was established for finding and treating latent TB infection among three groups of new refugees: from the former Soviet Union (FSU), former Yugoslavia (FY), and Somalia. RESULTS: From July 1999 through December 2000, treatment was offered to 442 refugees, of whom 389 (88%) started and 319 (82%) completed therapy. The completion rate among starters from the FSU was 76%, for those from FY it was 94% and for those from Somalia it was 88%. Among all refugees to whom treatment was offered, 319/442 (72%) completed therapy. CONCLUSION: Cultural case management may be a useful tool for expanding treatment of latent TB infection among foreign-born individuals.

Antitubercular Agents↗
PubMed2003

IGF-1 receptor mediates differentiation of primary cultures of mouse skeletal myoblasts.

Studies involving immortalized myoblasts suggested that insulin-like growth factors (IGFs) promote differentiation of skeletal muscle, but gene targeting experiments in mice did not provide support for this hypothesis. To address this discrepancy, we examined differentiation of primary cultures of mouse myoblasts. Differentiation was normally unaffected by addition of IGFs to the differentiation medium. However, when we interrupted IGF-mediated signaling, by incubating myoblasts with suramin or with a monoclonal antibody to the IGF-I receptor, differentiation was inhibited. Inhibition was reversed by exogenous IGF-I or IGF-II, but not by insulin. Differentiation was enhanced in myoblasts that were incubated with an inhibitor of the mitogen-activated protein kinase signaling pathway (PD098059) and such cells were responsive to exogenous IGF-I. Our results demonstrate that IGF action contributes to the differentiation of non-immortalized mouse myoblasts and that these cells represent a model system that can be experimentally manipulated to study the molecular events involved in skeletal muscle differentiation.

Animals↗
PubMed2003

Analysis of the frequency distribution of tuberculin skin test readings: a tool for the assessment of group contact investigations.

SETTING: The public health tuberculosis control program covering Seattle, Washington, and its surrounding suburban areas. OBJECTIVE: To describe a tool of potential usefulness in the assessment of transmission of tuberculosis in contact investigations of groups, such as co-workers or schoolmates of an infectious case, with a low prior probability of latent tuberculosis infection (LTBI). DESIGN: Tuberculin skin test (TST) readings in mm of the group being tested were graphed and compared with the known frequency distributions of TST readings of populations with and without LTBI, the latter including a fraction with non-specific tuberculin reactivity. RESULTS: Four group contact investigations were analyzed retrospectively with this tool. In two the graphed TST readings of contacts fell within the distribution of a population with LTBI, and suggested that transmission had occurred. In the other two, the graphed readings better fit the distribution of a population with non-specific tuberculin reactivity and suggested that transmission had not occurred. CONCLUSION: This simple tool to facilitate the determination of whether transmission of tuberculosis has occurred, and who should be offered treatment for LTBI in contact investigations of groups of people, deserves further study.

Adolescent↗
PubMed2002

Zebrafish insulin-like growth factor-I receptor: molecular cloning and developmental expression.

The biological actions of the insulin-like growth factors (IGFs) are mediated primarily by the IGF-I receptor (IGF-IR), and the IGF family has been highly conserved throughout vertebrate evolution. In this study we report the isolation of a 3 kb cDNA clone for the zebrafish IGF-IR that includes the complete 3' untranslated region and polyA tail and mapping of the receptor gene to zebrafish linkage group 7. The open reading frame deduced from the cDNA sequence encompasses the juxtamembrane and protein tyrosine kinase portions of the receptor, and is 70 and 67% identical to the corresponding regions of the IGF-IRs of the turbot and Xenopus, respectively. By RT-PCR, zebrafish IGF-IR expression was detected from early blastula to early larval stages of development. Using whole mount in situ hybridization, IGF-IR expression was detected after gastrulation. Expression was evident in most tissues but was particularly evident in the tail, in eye and ear primordia and in the brain.

3' Untranslated Regions↗
PubMed2002

Treatment of isoniazid-resistant tuberculosis with isoniazid, rifampin, ethambutol, and pyrazinamide for 6 months.

SETTING: In 1992 the Seattle-King County Department of Public Health Tuberculosis Clinic began to treat patients with isoniazid-resistant tuberculosis with a regimen of isoniazid, rifampin, pyrazinamide, and ethambutol daily for 6 months. OBJECTIVE: To conduct a review of clinical and bacteriological outcomes of treatment for patients who received the four-drug, 6-month regimen for isoniazid-resistant tuberculosis. DESIGN: A retrospective review of medical records of TB cases meeting the study criteria, a Mycobacterium tuberculosis isolate resistant to isoniazid, and intent to treat with a 6-month course of isoniazid, rifampin, pyrazinamide, and ethambutol. RESULTS: Through December 1999, 44 consecutive patients with isoniazid-resistant, rifampin-susceptible tuberculosis were started on the four-drug, 6-month daily regimen. Among 42 patients followed until completion of therapy, three required changes in the regimen due to side effects. There was one case of drug-induced hepatotoxicity. Among 39 patients with pulmonary involvement, 37 converted sputum cultures from positive to negative within 2 months of starting treatment. There were no treatment failures. On passive follow-up of at least 2 years on all patients, two patients relapsed. The single patient with bacteriological relapse did not develop further drug resistance. CONCLUSION: The regimen of isoniazid, rifampin, pyrazinamide, and ethambutol given daily for 6 months produced successful outcomes when used in a public health tuberculosis clinic as routine therapy for isoniazid-resistant tuberculosis.

Adolescent↗
PubMed2001

Monotreme IGF2 expression and ancestral origin of genomic imprinting.

IGF2 (insulin-like growth factor 2) and M6P/IGF2R (mannose 6-phosphate/insulin-like growth factor 2 receptor) are imprinted in marsupials and eutherians but not in birds. These results along with the absence of M6P/IGF2R imprinting in the egg-laying monotremes indicate that the parental imprinting of fetal growth-regulatory genes may be unique to viviparous mammals. In this investigation, we have cloned IGF2 from two monotreme mammals, the platypus and echidna, to further investigate the origin of imprinting. We report herein that like M6P/IGF2R, IGF2 is not imprinted in monotremes. Thus, although IGF2 encodes for a highly conserved growth factor in chordates, it is only imprinted in therian mammals. These findings support a concurrent origin of IGF2 and M6P/IGF2R imprinting in the late Jurassic/early Cretaceous period. The absence of imprinting in monotremes, despite apparent interparental conflicts over maternal-offspring exchange, argues that a fortuitous congruency of genetic and epigenetic events may have limited the phylogenetic breadth of genomic imprinting to therian mammals. J. Exp. Zool. (Mol. Dev. Evol.) 291:205-212, 2001.

Amino Acid Sequence↗
PubMed2001

Divergent evolution in M6P/IGF2R imprinting from the Jurassic to the Quaternary.

M6P/IGF2R imprinting first appeared approximately 150 million years ago following the divergence of prototherian from therian mammals. Although M6P/IGF2R is clearly imprinted in opossums and rodents, its imprint status in humans remains ambiguous. It is also still unknown if M6P/IGF2R imprinting was an ancestral mammalian epigenotype or if it evolved convergently. We report herein that M6P/IGF2R is imprinted in Artiodactyla, as it is in Rodentia and Marsupialia, but that it is not imprinted in Scandentia, Dermoptera and Primates, including ringtail lemurs and humans. These results are most parsimonious with a single ancestral origin of M6P/IGF2R imprinting followed by a lineage-specific disappearance of M6P/IGF2R imprinting in Euarchonta. The absence of M6P/IGF2R imprinting in extant primates, due to its disappearance from the primate lineage over 75 million years ago, demonstrates that imprinting at this locus does not predispose to human disease. Moreover, the divergent evolution of M6P/IGF2R imprinting predicts that the success of in vitro embryo procedures such as cloning may be species dependent.

Animals↗
PubMed2001

Imprint status of M6P/IGF2R and IGF2 in chickens.

Genomic imprinting is a method of gene regulation whereby a gene is expressed in a parent-of-origin-dependent fashion; however, it is hypothesized that imprinting should not occur in oviparous taxa such as birds. Therefore, we examined the allelic expression of two genes in the chicken that are reciprocally imprinted in most mammals, mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) and insulin-like growth factor 2 (IGF2). Single nucleotide polymorphisms were identified in these genes, and cDNA was prepared from several tissues of embryos heterozygous for these polymorphisms. Both alleles of M6P/IGF2R and IGF2 were expressed in all tissues examined by RT-PCR. Since the expression of these genes was independent of the parent from which they were inherited, we conclude that neither M6P/IGF2R nor IGF2 are imprinted in the chicken.

Animals↗
PubMed2000

Binding of 125I-insulin-like growth factor-II to cells cultured in fetal bovine serum: a complication.

Insulin-like growth factor II is an important fetal mitogen in mice and humans and its biological activity is regulated in a complex manner. The peptide interacts with three membrane-bound receptors, with a superfamily of insulin-like growth factor binding proteins and with the proteoglycan, glypican-3. Recently, the blood protein, vitronectin, has been identified as a novel insulin-like growth factor II-binding protein. Many studies have used cell lines maintained in fetal bovine serum to identify cell surface insulin-like growth factor II binding sites. We now describe a complication associated with the interpretation of such in vitro studies. Fetal bovine serum-derived vitronectin adheres very tightly to tissue culture dishes. When cells that have been maintained in fetal bovine serum are incubated with 125I-insulin-like growth factor II, a substantial fraction of the 125I-insulin-like growth factor II apparently associated with the cell surfaces may represent radioliogand bound by the fetal bovine serum-derived vitronectin. This may result in over-estimation of cell surface insulin-like growth factor II binding sites.

Animals↗
PubMed2000

Comparison testing of current (PPD-S1) and proposed (PPD-S2) reference tuberculin standards.

Since 1951, the tuberculin PPD-S1 has been used to standardize commercial PPD reagents and perform special tuberculin surveys. PPD-S1 is now in short supply and a new standard (PPD-S2) has been manufactured. To determine if PPD-S2 is equivalent and can replace PPD-S1, we conducted a double-blind clinical trial. Between May 14 and October 28, 1997, 69 subjects with a history of culture-proven tuberculosis (TB patients) and 1,189 subjects with a very low risk for TB infection were enrolled, received four skin tests (with PPD-S1, PPD-S2, and one each of the commercially available PPDs), and had reactions measured by two trained observers. Among the TB patients, we found statistically indistinguishable immunogenicity (mean reaction size +/- standard deviation): 15.6 +/- 6.6 mm for PPD-S1 and 14.8 +/- 5.6 mm for PPD-S2. Among low-risk subjects, the tests had equally high specificities (PPD-S1, 98.7% and PPD-S2, 98. 5%), using a 10-mm cutoff. The number of discordant (negative versus positive) interpretations for PPD-S2, assuming that low-risk subjects who had a >/= 10 mm reaction to PPD-S1 were truly infected, was low (0.5%) and indistinguishable from the rate of discordant interpretations of the same test when read by two different observers (0.8%). The study results indicate that PPD-S2 is qualified to be used as the new U.S. reference standard for PPD tuberculin.

Adult↗
PubMed1999

Hepatotoxicity associated with isoniazid preventive therapy: a 7-year survey from a public health tuberculosis clinic.

CONTEXT: Isoniazid preventive therapy for latent tuberculosis (TB) infection has been debated because of the risk of hepatotoxicity. The frequency of hepatotoxicity was 0.5% to 2.0% in early studies but may have changed with new criteria for diagnosis and patient selection. OBJECTIVE: To determine the rate of isoniazid hepatotoxicity in patients managed according to current guidelines and practice standards. DESIGN: Prospective cohort study. SETTING: A public health clinic operated by the TB control program of a city-county public health agency. PATIENTS: A total of 11141 consecutive patients who started a regimen of isoniazid preventive therapy for latent TB infection from January 1989 through December 1995. MAIN OUTCOME MEASURES: The rate of developing symptoms and signs of hepatotoxicity among all persons starting isoniazid preventive therapy, among all those completing therapy, and by age, sex, and race. RESULTS: Eleven patients (0.10% of those starting, and 0.15% of those completing treatment) had hepatotoxic reactions to isoniazid during preventive treatment. The rate of hepatotoxicity in persons receiving preventive therapy increased with increasing age (chi2 for linear trend = 5.22, P=.02) and there were trends toward increased rates in women (odds ratio [OR], 3.30; 95% confidence interval [CI], 0.87-12.45; chi2 = 3.28; P=.07) and in whites (OR, 2.60; 95% CI, 0.75-8.95; chi2 = 3.08; P=.08). CONCLUSIONS: The rate of isoniazid hepatotoxicity during clinically monitored preventive therapy was lower than has been reported previously. Clinicians should have greater confidence in the safety of isoniazid preventive therapy.

Adolescent↗
PubMed1999

Variable accumulation of insulin-like growth factor II in mouse tissues deficient in insulin-like growth factor II receptor.

The insulin-like growth factor II receptor mediates endocytosis of insulin-like growth factor II, resulting in growth factor degradation in lysosomes. This degradation is an important regulator of growth factor activity in vivo, as shown by the phenotype of receptor deficient mice. Recent evidence suggests that the insulin-like growth factor II receptor functions as a tumour suppressor in humans, and that loss of receptor function leads to increased levels of the growth factor in tumours. It is difficult to establish such a causal relationship in human tumours however, since most tumours have undergone several genetic changes by the time they are examined. Using mouse embryos deficient in receptor expression, and an insulin-like growth factor II-specific radioimmunoassay, we tested the hypothesis that lack of receptor function leads to local accumulation of insulin-like growth factor II. We found that mutant blood and skeletal muscle had excess insulin-like growth factor II, but that mutant lungs and liver had no accumulation. Mutant hearts had less growth factor than wild-type hearts, an unexpected observation, since the normal embryonic heart expresses very high levels of insulin-like growth factor II receptor, and mutant mice apparently die of congestive heart failure. The placentas of mutant mice were larger than those of wild-type, but this did not correlate with an excess of placental insulin-like growth factor II. These results indicate that lack of insulin-like growth factor II receptor can lead to local excess of the growth factor but that such excess is not a necessary consequence of receptor-deficiency.

Animals↗
PubMed1999

Community-wide implementation of targeted testing for and treatment of latent tuberculosis infection.

Treatment of latent infection due to Mycobacterium tuberculosis will likely increase in importance as a strategy to prevent tuberculosis in the United States. This review was undertaken to assess how targeted testing and treatment of latent tuberculosis infection are currently organized, with a focus on the extension of those services from public health clinics to other community sites. Targeted testing programs are now being implemented in primary care neighborhood clinics, syringe-exchange programs, jails, and teen health clinics. Organizational issues at those new sites include the need for a tracking system for clinical follow-up and for incentives to promote adherence. There is increasing experience with directly observed treatment of latent tuberculosis infection. Communities that receive large numbers of immigrants and refugees should prioritize the evaluation of those whose chest radiographs are suggestive of tuberculosis. Current studies continue to point out imperfections in the current tools, such as the tuberculin skin test and isoniazid. Finally, the advent of managed care, especially for Medicaid recipients, presents both opportunities and challenges for expansion of population-based preventive health services.

Emigration and Immigration↗
PubMed1999

Four-month, four-drug preventive therapy for inactive pulmonary tuberculosis.

Standard preventive therapy for inactive pulmonary tuberculosis (TB) is 12 mo of isoniazid. Shorter multiple-drug preventive regimens have been proposed. From December 1993 through January 1996 we evaluated a 4-mo, four-drug regimen of preventive therapy for patients with inactive TB, mostly newly arriving immigrants from countries with high rates of TB and of isoniazid resistance. Fifty-three evaluable patients received a 4-mo regimen of isoniazid, rifampin, ethambutol, and pyrazinamide. We compared their completion rate, side effects, and cost of treatment with those of 108 age-matched patients who had received 12 mo of isoniazid at an earlier time. Sixty-eight percent of patients on the 4-mo regimen completed treatment; 69% of those on the 12-mo regimen completed treatment (p = 0.9393). Side effects were more frequent for the 4-mo regimen (30.2%) compared with 12 mo of isoniazid (11.1%) (p = 0. 0027). The cost of providing an uncomplicated, self-supervised regimen was estimated to be almost four times greater for the four-drug regimen compared with isoniazid. These results show that, in terms of compliance, a four-drug, 4-mo regimen had no advantage over standard preventive therapy for persons with inactive pulmonary TB. On the other hand, the shorter, more intensive regimen was associated with more frequent adverse effects and was more costly.

Adult↗
PubMed1998

Risk factors for pediatric tuberculosis infection and disease after household exposure to adult index cases in Alaska.

OBJECTIVES: To determine risk factors for pediatric tuberculosis infection and active tuberculosis. STUDY DESIGN: We examined medical records from multiple sources for all 282 children younger than 15 years in Alaska during the period 1987 to 1994 who were household contacts of an adult with culture-positive pulmonary tuberculosis. RESULTS: Infection developed in 25% of the children and progressed to active disease in 9.6%. Risk factors for pediatric infection included exposure to a parent who had active tuberculosis and exposure to any adult with active tuberculosis who had a cough, smear positivity, or a left upper lobe (LUL) chest lesion (odds ratios, 2.1 to 2.8). Among the 71 children in whom infection developed, Alaska Natives and younger children were more likely to progress to active tuberculosis, as were children exposed to a parent who had active tuberculosis and children exposed to any adult who had a LUL chest lesion (odds ratios, 1.5 to 12). CONCLUSIONS: Although all children with household exposure to adults with active tuberculosis have a high risk of contracting the infection and disease, specific risk factors can be identified and differ for infection and disease. Alaska Natives have an increased risk of progression to disease once infected.

Adolescent↗
PubMed1997

Influence of polymorphic N-acetyltransferase phenotype on the inhibition and induction of acetaminophen bioactivation with long-term isoniazid.

OBJECTIVE: To determine in patients receiving isoniazid prophylaxis whether an increase in the CYP2E1 dependent formation clearance of acetaminophen (paracetamol) to N-acetyl-p-benzoquinone imine (NAPQI) occurs during a normal 24-hour isoniazid dose interval and whether the interaction is dependent on acetylation status. METHODS: Acetaminophen elimination kinetics were determined on four different occasions. Ten subjects were assigned to receive acetaminophen either simultaneously with the 8 am dose of isoniazid or 12 hours after the isoniazid dose. One week later, on the last day of isoniazid therapy, subjects received acetaminophen at the alternate time of day. The control phase acetaminophen administrations were repeated 1 and 2 weeks later, following the initial randomization. Isoniazid acetylation (NAT2) genotype was determined by analysis of genomic DNA obtained from peripheral blood leukocytes. RESULTS: The mean NAPQI formation clearance was inhibited 57% when acetaminophen and isoniazid were coadministered but was unchanged compared with time-matched control when acetaminophen was given 12 hours after the isoniazid dose. However, when data from subjects was segregated according to isoniazid (INH) acetylation phenotype, the mean ratio of NAPQI formation clearances (+INH/-INH) with 8 PM acetaminophen was significantly higher for fast acetylators compared with slow acetylators (1.36 versus 0.68; p = 0.006). CONCLUSIONS: Fast metabolizers of isoniazid appeared to clear the inducer or inhibitor from the active site of CYP2E1 more rapidly, which resulted in an increased formation of NAPQI 12 hours after the isoniazid dose. In contrast, formation of NAPQI for slow isoniazid metabolizers remained inhibited.

Acetaminophen↗