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Biomedical subjects

N M Graham

Publications and source records attributed to N M Graham.

At least 19 recordsLinked to original sources
PubMed2006

3-5 year longitudinal follow-up of pediatric patients after acute renal failure.

Few data exist regarding the long-term sequelae of acute renal failure (ARF), and these studies are limited to a few renal conditions. We aim to assess the 3-5-year survival and incidence of renal injury in children who previously developed ARF of varying causes. We queried parents, physicians, and hospital/state vital statistics records to find patient survival in 174 children who previously had ARF and survived to hospital discharge. We assessed the following in 29 children for residual renal injury: (a) microalbuminuria, (b) glomerular filtration rate (GFR) by Schwartz formula, (c) hypertension, and (d) hematuria. The 3-5-year survival of children with ARF who survived to hospital discharge was 139/174 (79.9%). Most deaths (24/35 (68.5%)) occurred within 12 months after initial hospitalization. Combining those who died during initial hospitalization and in subsequent 3-5 years, the overall survival rate was 139/245 (56.8%). In all, 16 children progressed to end-stage renal disease; thus, renal survival was 127/173 (91%). Those with primary renal/urologic conditions had lower renal survival than others (24/35 (68.6%) vs 134/139 (96.4%); P<0.0001). Among the 29 patients assessed for long-term sequelae at 3-5 years, 17/29 (59%) subjects had at least one sign of renal injury; microalbuminuria (n=9), hyperfiltration (n=9), decreased GFR (n=4), and hypertension (n=6). A pediatric nephrologist was involved in care of only 6/17 (35%) with chronic renal injury. Patients have high risks of ongoing residual renal injury and death after ARF; therefore, periodic evaluation after the initial insult is necessary.

Acute Kidney Injury↗
PubMed2004

The use of structural proximal femoral allografts in complex revision hip arthroplasty.

Between April 1992 and November 1998 we used 34 massive proximal femoral allografts for femoral reconstruction at revision hip arthroplasty. Seven patients have died and two have been lost to follow-up. There were thus 25 grafts in 24 patients for review. The mean follow-up was 53 months (16 to 101). By the time of the review two patients had undergone a further revision for failure of the allograft. Another had required secondary plating and grafting at the graft-host junction for symptomatic nonunion. One had recurrence of deep sepsis and was being managed conservatively. Trochanteric union was considered to have occurred radiologically in 16 of the 25 grafts and union at the host-graft junction in 20. Resorption of the allograft was significant in only two hips. We recommend this technique in cases in which femoral bone loss has been catastrophic.

Adult↗
PubMed2001

Isoniazid preventive therapy, hepatitis C virus infection, and hepatotoxicity among injection drug users infected with Mycobacterium tuberculosis.

Treatment of latent Mycobacterium tuberculosis infection with isoniazid can cause hepatotoxicity, but the risk of isoniazid-associated hepatotoxicity among persons coinfected with hepatitis C virus (HCV) is unknown. We conducted a prospective study among 146 injection drug users with M. tuberculosis infection and normal baseline hepatic transaminase values who were treated with isoniazid. Of 146 participants, 138 (95%) were HCV-seropositive. Thirty-seven participants (25%) were human immunodeficiency virus (HIV)-seropositive. Thirty-two (22%; 95% confidence interval [CI], 16%-30%) of 146 participants developed transaminase value elevations to >3 times the upper limit of normal. Transaminase value elevation was associated with concurrent alcohol use but not with race, age, presence of hepatitis B surface antigen, HIV-1 infection, or current injection drug use. Isoniazid was withdrawn from 11 participants (8%; 95% CI, 4%-13%). Of 8 deaths during follow-up, none were attributed to isoniazid-associated hepatotoxicity. The risk of transaminase value elevation and drug discontinuation for HCV-infected persons receiving isoniazid was within the range reported for populations with lower HCV prevalence.

Adult↗
PubMed2001

Zidovudine and stavudine sequencing in HIV treatment planning: findings from the CHORUS HIV cohort.

BACKGROUND: Optimal sequencing of zidovudine and stavudine in antiretroviral therapy has not been elucidated. OBJECTIVE: To examine the impact of the sequence of therapeutic regimens containing zidovudine and stavudine on HIV-1 RNA and CD4 lymphocyte counts over 12 months. DESIGN: Observational, multicenter, longitudinal cohort study. SETTING: Four large outpatient, HIV practices participating in the community-based Collaborations in HIV Outcomes Research-U.S. (CHORUS) cohort study. PARTICIPANTS: 940 HIV-infected patients. METHODS: Comparison of HIV-1 RNA and CD4 lymphocyte responses in patients sequenced from zidovudine to stavudine or from stavudine to zidovudine using repeated measures regression models fit to outcomes by application of generalized estimating equation (GEE) methodology. RESULTS: Patients treated with zidovudine prior to stavudine (n = 834) achieved a greater mean drop from baseline HIV-1 RNA (p = .01) and higher proportion of undetectable HIV-1 RNA results (p = .05) over 12 months than those sequenced from stavudine to zidovudine (n = 106). CD4+ lymphocyte increases did not differ between the groups (p = .6). CONCLUSIONS: Prior zidovudine therapy was not associated with long-term attenuation of HIV-1 RNA or CD4 response to subsequent stavudine-containing regimens. Zidovudine before stavudine may have benefit in a strategic long-term therapeutic plan.

Adolescent↗
PubMed2000

Metabolic disorders among HIV-infected patients treated with protease inhibitors: a review.

Currently available protease inhibitors are associated with development of a group of metabolic disorders. These include a peripheral lipodystrophy syndrome in which there is fat wasting in the face, arms, and legs; fat accumulation in the abdomen, dorsocervical region, and/or breasts (women only); as well as hyperlipidemia, hypercholesterolemia, and insulin resistance. A review of 15 observational studies and case reports shows that the incidence of the peripheral lipodystrophy syndrome increases with time of exposure to protease inhibitors, with a >60% incidence seen after 1 year of continuous treatment. Protease inhibitors are hypothesized to cause this syndrome by impairing conversion of retinoic acid to cis-9-retinoic acid (leading to impaired peripheral fat storage, sequestration of body fat to central adipocytes, and hyperlipidemia) and by inhibiting low-density lipoprotein receptor-related protein (LRP), thus preventing postprandial chylomicron clearance and further contributing to hyperlipidemia. Recent in vitro data suggest that more than one pathway contributes to the lipodystrophy syndrome and that pathways may differ among protease inhibitors. Although the central fat accumulation, hyperlipidemia, and insulin resistance components of this syndrome may reverse after discontinuation of protease inhibitor therapy, it is not known whether complete normalization of fast-wasted body regions is possible. Prospective controlled studies are needed to define whether protease inhibitors currently under development are less prone to produce the lipodystrophy syndrome.

Drug Therapy, Combination↗
PubMed2000

Histologic development of cervical ectopy: relationship to reproductive hormones.

BACKGROUND AND OBJECTIVES: Cervical ectopy has been proposed as a risk factor for chlamydial infection, HIV, and other sexually transmitted diseases (STDs). Ectopy is a histologic phenomenon resulting from a complex interplay of morphologic and hormonal processes. Reproductive hormones influence the production of ectopy during late fetal life, puberty, pregnancy, and with use of oral contraceptives. Ectopy is modified over time by squamous metaplasia and epitheliazation, low pH, trauma, and possibly by cervical infection. STUDY DESIGN: The authors review the histologic development of ectopy from late fetal life to menopause to understand STD risk. RESULTS: Ectopy is often assessed and quantified by direct, unaided observation during speculum examinations. This method may result in inaccurate estimates and misclassification with the transformation zone. CONCLUSION: Valid, reproducible measures of ectopy are necessary for epidemiologic studies to examine the impact of exogenous hormonal contraceptives on the development of ectopy and on potential infection risk.

Adolescent↗
PubMed2000

Relationship of hormonal contraception and cervical ectopy as measured by computerized planimetry to chlamydial infection in adolescents.

BACKGROUND: Adolescents are at increased risk for chlamydial infection and its sequelae. Hormonal contraception and cervical ectopy were previously suggested risk factors for chlamydia. GOAL: To determine if chlamydia is more prevalent in female participants with greater ectopy and in hormonal contraceptive users. STUDY DESIGN: Ninety-seven adolescent females aged 11 to 20 years were recruited from two Baltimore inner-city clinics. After administering a reproductive history questionnaire, endocervical specimens were tested for Chlamydia trachomatis by polymerase chain reaction. After acetic acid application to the cervix, cervical photographs were taken, the area of ectopy was quantified by computerized planimetry, and ectopy was categorized as none (0mm2), mild (< 22mm2), and moderate (> 22mm2). The likelihood of chlamydia by ectopy and type of hormonal contraceptive use was determined by logistic regression adjusted for age and sexual partners. RESULTS: The odds of chlamydial infection was similar in persons with mild ectopy compared with no ectopy (adjusted odds ratio [OR], 0.76; 95% CI, 0.14-4.03), and in persons with moderate ectopy compared with no ectopy (adjusted OR, 1.94; 95% CI, 0.40-9.39). The likelihood of chlamydia was higher in depot-medroxyprogesterone acetate users compared with nonhormone users (adjusted OR, 5.44; 95% CI, 1.25-23.6). Oral contraceptive users did not have an increased likelihood of chlamydia (adjusted OR, 0.92; 95% CI, 0.10-8.78). CONCLUSION: Using a new, reliable, and standardized technique to quantify cervical ectopy, the authors did not find an elevated prevalence of chlamydial infection in adolescents with cervical ectopy. Depot-medroxyprogesterone acetate use may increase the risk of chlamydial infection compared with combined estrogen-progestin oral contraceptives.

Adolescent↗
PubMed1999

Virologic, immunologic, and immune activation markers as predictors of HIV-associated weight loss prior to AIDS. Multicenter AIDS Cohort Study.

OBJECTIVES: To study weight patterns among HIV-positive men and associations of baseline HIV RNA, CD4+ lymphocyte count, and serum levels of neopterin and beta2-microglobulin with subsequent weight loss prior to AIDS. METHODS: A cohort of 1558 homosexual men from the Multicenter AIDS Cohort Study comprised the main study population. Marker values obtained using samples from a baseline visit in 1984 to 1985 were associated with weight patterns and risk of weight loss events over 10 years of follow-up. To investigate the impact of protease inhibitor (PI) therapy on weight patterns, a separate analysis was conducted for men who initiated such therapy in 1995 to 1996. RESULTS: In general, HIV-positive men demonstrated a striking tendency toward weight loss, with a rate of decline that increased over time. Distinct variations in this pattern were observed according to baseline HIV RNA levels. Each marker considered was independently predictive of weight loss events. Following use of PIs, 68 men showed a tendency toward increased weight, compared with men who did not use PIs. CONCLUSIONS: Although baseline virologic, immunologic, and immune activation markers all predicted weight loss events in AIDS-free HIV-positive men, HIV RNA displayed the best discrimination. Shifts in weight patterns observed in this cohort after PI therapy call for further attention to nutritional and body changes as the duration of therapy increases.

Adult↗
PubMed1999

Cervical ectopy and the transformation zone measured by computerized planimetry in adolescents.

OBJECTIVE: To determine whether cervical ectopy and the transformation (T) zone were larger in adolescents using oral contraceptives (OCs) compared to depot medroxyprogesterone acetate (DMPA). METHOD: Cervical photographs were taken on 91 adolescents in Baltimore, Maryland. Ectopy and T zone size were measured using computerized planimetry. Patients provided reproductive and sexual history. Correlates of ectopy and T zone size were identified by proportional odds and linear regression models, respectively. RESULT: Twenty-five women had no ectopy. Parity was independently associated with greater ectopy (OR 3.9, 95% CI 1.37-11.11). Predictors of smaller ectopy were douching (OR 0.23, 95% CI 0.09-0.65), and shorter sexual history (OR 0.20, 95% CI 0.05-0.74). Neither OC or DMPA were associated with ectopy. Predictors of greater T zone size were years since menarche (13.8 mm2/year, P = 0.003) and OCs (54.7 mm2, P = 0.05). DMPA predicted a smaller T zone (-67.0 mm2, P = 0.01). CONCLUSION: Computerized planimetry provides standardized measurements. Douching and sexual activity may decrease ectopy through increased squamous metaplasia. Hormonal contraceptives were not associated with ectopy in adolescents. However, long-term progestin use may decrease T zone size.

Adolescent↗
PubMed1999

Cell-associated infectious HIV-1 viral load as a predictor of clinical progression and survival among HIV-1 infected injection drug users and homosexual men.

Cell-associated infectious HIV-1 viral load was measured using semi-quantitative microculture techniques to determine its predictive capability for progression to AIDS or survival among HIV-1 infected injecting drug users (IDU) and homosexual men (HM). The authors followed 296 IDU and 240 HM from February 1992 through September 1995 for: (i) death, (ii) AIDS, and (iii) AIDS or bacterial infection. At baseline, viral load was quantified using microculture techniques to determine infectious units per million peripheral blood mononuclear cells (IUPM). Data were analyzed using standard statistical methods for survival analysis. Of the 536 total participants, 106 died (20%), and 98 of the 481 AIDS-free participants developed AIDS (20%). The relative hazard of AIDS for a viral load of > or = 100 IUPM, relative to a negative culture (0 IUPM), was 6.73 (95% CI: 2.23-20.3) after adjusting for risk group, initial CD4+ count, and other covariates. The adjusted relative hazard of death for a viral load of > or = 100 IUPM vs. 0 IUPM was 2.57 (95% CI: 0.97 6.80). Viral load predicted time to death within the < 200 cells/ul CD4+ stratum. The predictive value of viral load on HIV-1 progression did not vary by risk group. These data show that cell associated infectious HIV-1 viral load was significantly predictive of progression across risk groups for AIDS and death among those severely immune compromised.

AIDS-Related Opportunistic Infections↗
PubMed1999

Unrecognised transmission of tuberculosis in prisons.

BACKGROUND: Tuberculosis (TB) is a public health concern in correctional facilities. High turnover of inmate populations may preclude timely diagnosis of TB, so that unrecognised transmission may be common. OBJECTIVE: To determine the proportion of inmates with new skin test conversions who had identifiable exposure to diagnosed cases of TB in the correctional system, and to test the hypothesis that source cases of TB may be undiagnosed during incarceration. SETTING: Maryland Division of Corrections, USA. SUBJECTS: All inmates whose skin test converted from negative to positive at annual screening. DESIGN: All cases of TB in inmates, diagnosed in the prisons during the relevant time period, were identified. Movements of skin test converters and potential source cases within the prisons were matched. We then matched all inmates discharged from the prison system with all new cases of tuberculosis notified to the Maryland Department of Health & Mental Hygiene tuberculosis registry in 1994. RESULTS: The inmate turnover was 21% per year. Probable exposure to a diagnosed source case was found in 13% of converters, possible exposure in 10% and no exposure in 72%. In a further 5% exposure status could not be determined. We identified four cases of pulmonary tuberculosis notified to the state in 1994, within 3 months of discharge in released inmates, who were not known to have tuberculosis whilst incarcerated. CONCLUSIONS: Significant transmission of TB due to undiagnosed index cases may occur in prisons due to high population turnover. New skin test conversions in inmates should be treated as new infection, even in the absence of identifiable exposure to TB.

Contact Tracing↗
PubMed1999

Comparison between a whole blood interferon-gamma release assay and tuberculin skin testing for the detection of tuberculosis infection among patients at risk for tuberculosis exposure.

A new test that measures interferon-gamma (IFN-gamma) release in whole blood following stimulation with tuberculin has the potential to detect tuberculosis infection using a single blood draw. The IFN-gamma release assay was compared with the standard tuberculin skin test (TST) among 467 intravenous drug users at risk for tuberculosis in urban Baltimore. Among 300 human immunodeficiency virus (HIV)-seronegative patients, the IFN-gamma release assay was positive in 177 (59%), whereas the TST was positive in 71 (24%), for a percent agreement of 59% (kappa=26%). Among 167 HIV-seropositive subjects, the IFN-gamma release assay identified 32 reactors (19%); the TST identified 16 reactors (9.6%), for a percent agreement of 82% (kappa=28%). The IFN-gamma release assay detected more reactors than did the TST, but its agreement with TST was weak. As the TST is an imperfect standard, further evaluation of the IFN-gamma release assay among uninfected persons and persons with culture-confirmed tuberculosis will be useful.

Evaluation Studies as Topic↗
PubMed1998

Molecular and geographic patterns of tuberculosis transmission after 15 years of directly observed therapy.

CONTEXT: Recent studies suggest that one third of tuberculosis cases in urban areas result from recent transmission. Improved tuberculosis control measures such as uniform implementation of directly observed therapy might reduce the proportion of cases resulting from recent transmission. OBJECTIVE: To determine patterns of tuberculosis transmission in Baltimore, Md, after 15 years of community-based directly observed therapy. DESIGN: A 30-month (January 1994-June 1996), prospective, city-wide study of all cases of tuberculosis using traditional contact investigations, geographic information systems data, and molecular epidemiologic comparison of Mycobacterium tuberculosis isolates with 2 DNA probes. PATIENTS: One hundred eighty-two patients with culture-positive tuberculosis. MAIN OUTCOME MEASURES: Proportion of disease defined as recently transmitted based on epidemiologic linkage by traditional contact tracing and molecular linkage by DNA fingerprint analysis of isolates; geographic foci of transmission based on linkage of residences by geographic information systems data. RESULTS: Of the 182 patients who had isolates of M tuberculosis available, 84 (46%) showed molecular clustering with 58 (32%) defined as being recently transmitted. Only 20 (24%) of 84 cases with clustered DNA fingerprints had epidemiologic evidence of recent contact. Geographic analysis showed significant spatial aggregation of the 20 clustered cases with epidemiologic links (P<.001), occurring in areas of low socioeconomic status and high drug use. The 64 cases with clustered DNA fingerprints but without epidemiologic links shared common risk factors and demographic features with the 20 clustered patients who did have epidemiologic links. CONCLUSIONS: Recently transmitted tuberculosis accounts for a high proportion of tuberculosis cases in Baltimore. Recently transmitted cases occur in geographically distinct areas of Baltimore, and location-based control efforts may be more effective than contact tracing for the early identification of cases.

Adult↗
PubMed1998

Mycobacterium tuberculosis infection and disease are not associated with protection against subsequent disseminated M. avium complex disease.

OBJECTIVE: To determine the relationship between Mycobacterium tuberculosis infection and disease and subsequent disseminated M. avium complex (MAC) disease in HIV-infected persons. DESIGN: A prospective observational cohort study. SETTING: The AIDS Linked to the Intravenous Experience (ALIVE) cohort of injecting drug users and the Johns Hopkins Hospital Adult HIV Clinic (JHHAHC). PARTICIPANTS: HIV-infected persons aged > 18 years with CD4 lymphocytes < 100 x 10(6)/l were followed between July 1989 and 31 October 1996. There were 182 persons in the ALIVE cohort and 1129 persons in JHHAHC who met these criteria. MAIN OUTCOME MEASURE: The relative risk of disseminated MAC was determined according to a history of prior opportunistic infection, MAC prophylaxis, antiretroviral therapy, M. tuberculosis infection or disease, race, sex, and injecting drug use. RESULTS: Amongst the 30 patients with active tuberculosis, eight developed disseminated MAC, compared with 208 cases of disseminated MAC amongst 1148 patients without prior M. tuberculosis infection or disease [relative risk (RR), 1.5; 95% confidence interval (CI), 0.8-2.7; P=0.2]. Amongst the 10 patients with extrapulmonary tuberculosis, five developed disseminated MAC (RR, 2.8; 95% CI, 1.5-5.2; P=0.02). Injecting drug use was associated with a decreased risk of disseminated MAC (RR, 0.7; 95% CI, 0.6-0.9; P=0.007). In a logistic regression analysis, disseminated MAC was significantly associated with extrapulmonary tuberculosis and other opportunistic disease, whereas antibiotic prophylaxis and injecting drug use were protective. CONCLUSIONS: A history of M. tuberculosis infection or disease was not associated with protection against subsequent disseminated MAC disease in HIV-infected persons. However, persons with extrapulmonary tuberculosis were at increased risk for disseminated MAC, particularly at low CD4 cell levels.

AIDS-Related Opportunistic Infections↗
PubMed1998

Health services use by urban women with or at risk for HIV-1 infection: the HIV Epidemiology Research Study (HERS).

OBJECTIVE: To characterize health services use by urban women with or at risk for HIV-1 infection enrolled in a prospective multicenter study. METHODS: 1310 women 16 to 55 years of age who were at risk for HIV-1 infection were recruited between April 1993 and January 1995 at four urban centers (Baltimore, Maryland; The Bronx, New York; Detroit, Michigan; and Providence, Rhode Island). HIV-1-seropositive women without AIDS-defining illness were oversampled in a ratio of 2:1 in comparison with HIV-1-seronegative women. At a baseline study visit, the women received physical and laboratory examinations, including CD4+ counts, and were interviewed regarding HIV risk behavior, health services use, and clinical data. RESULTS: 863 women were HIV-1-seropositive and 430 were HIV-1-seronegative. Fifty-two percent of the women reported injection drug use (IDU) since 1985, and 48% acquired HIV through sexual contact. Seventy-seven percent were African American, 23% were white, and 16% were Hispanic. The median age was 35 years. HIV-seronegative women were significantly less likely to have health insurance (19%) than were HIV-seropositive women (30%; p < .001). Among the HIV-seropositive women, 68% had CD4+ cell counts of <500/microl, and 64% were asymptomatic. Sixty-four percent of the HIV-seronegative women had had an outpatient hospital visit in the past 6 months, as had 86% of HIV-seropositive women (p < 0.001). Hospitalization in the past 6 months was also higher in HIV-seropositive women (22% vs. 12%; p < .001). Despite heavy use of health services, only 49% of women with CD4+ counts of <200/microl reported current use of antiretroviral therapy, and only 58% reported current use of Pneumocystis carinii pneumonia (PCP) prophylaxis. Among HIV-seropositive women, and after adjusting for CD4+ count, HIV symptoms, race, and study site, IDUs were significantly less likely to have a regular doctor and a recent outpatient visit and more likely to be hospitalized and use the emergency department (ED) than were non-IDUs. In multivariate analyses of HIV-seropositive persons, African American women had similar access to care and use of antiretroviral therapy and PCP prophylaxis than did white women but were less likely to have an outpatient department visit in the previous 6 months and to be taking PCP and opportunistic infection (OI) prophylaxis. Health services access and use of HIV-related therapies did not significantly differ between Hispanic and white women with HIV infection. CONCLUSION: Although both HIV-seropositive and HIV-seronegative women had high levels of use of medical services, current use of antiretrovirals and OI prophylaxis was low throughout, and IDUs used HIV-related primary health services less and were more likely to receive emergency or episodic care. IDU and African American race were independently associated with decreased use of medical services.

Adolescent↗
PubMed1998

Studies of antiretroviral therapy in the Multicenter AIDS Cohort Study.

The Food and Drug Administration has been increasingly reliant on surrogate end points to fast-track the licensing of antiretroviral agents. As a result, critical information, such as long-term adverse events, clinical progression rates, survival, and development of resistance, are not available before licensure. Therefore, phase IV studies conducted in large community- and/or clinic-based cohorts will become essential to fill in the gaps in the clinical knowledge base for many of these drugs, and observational cohort studies of HIV-infected patients have been used to address many of these questions. In addition to studies of antiretroviral impact on adverse events and outcomes, such cohorts can provide valuable data on utilization patterns, physician prescribing patterns, and the important issue of patient compliance with increasingly complicated drug regimens.

AIDS-Related Opportunistic Infections↗