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Biomedical subjects

K McAdam

Publications and source records attributed to K McAdam.

At least 19 recordsLinked to original sources
PubMed2005

Investigation of the risk factors for tuberculosis: a case-control study in three countries in West Africa.

BACKGROUND: Host-related and environment-related factors have been shown to play a role in the development of tuberculosis (TB), but few studies were carried out to identify their respective roles in resource-poor countries. METHODS: A multicentre case-control study was conducted in Guinée, Guinea Bissau, and The Gambia, from January 1999 to March 2001. Cases were newly detected smear positive TB patients. Two controls were recruited for each case, one within the household of the case, and one in the community. RESULTS: Regarding host-related factors, univariate analysis by conditional logistic regression of 687 matched pairs of cases and household controls showed that TB was associated with male sex, family history of TB, absence of a BCG scar, smoking, alcohol, anaemia, HIV infection, and history and treatment of worm infection. In a multivariable model based on 601 matched pairs, male sex, family history of TB, smoking, and HIV infection were independent risk factors of TB. The investigation of environmental factors based on the comparison of 816 cases/community control pairs showed that the risk of TB was associated with single marital status, family history of TB, adult crowding, and renting the house. In a final model assessing the combined effect of host and environmental factors, TB was associated with male sex, HIV infection, smoking (with a dose-effect relationship), history of asthma, family history of TB, marital status, adult crowding, and renting the house. CONCLUSION: TB is a multifactorial disorder, in which environment interacts with host-related factors. This study provided useful information for the assessment of host and environmental factors of TB for the improvement of TB control activities in developing countries.

Adult↗
PubMed2005

Humoral response to Mycobacterium tuberculosis antigens in patients with tuberculosis in the Gambia.

OBJECTIVE: To determine and compare the sensitivity and specificity of four common mycobacterial antigens with three RD-1 region antigens in the serological diagnosis of active pulmonary tuberculosis (PTB) in the Gambia. DESIGN: Serum from 300 Gambians (100 with active PTB, 100 of their household contacts, and 100 community controls) was tested using an ELISA method to detect antibodies to seven mycobacterial antigens (three encoded in the RD-1 region [ESAT-6, CFP-10 and Rv3871] and four common [38 kDa, GLU-S, 19 kDa and 14 kDa]). Individuals with active TB were recruited from one of the National Leprosy and TB Control Program clinics in the western region of the Gambia, and neighborhood controls were an age-matched individual living within five houses of the case. RESULTS: The sensitivity of the RD-1 antigens ranged from 34% to 67%, while specificity ranged from 51% to 71%. The sensitivity of the common antigens ranged from 24% to 75% and specificity from 26% to 75%. CONCLUSION: In countries with high rates of TB, such as the Gambia, the clinical utility of serological testing to diagnose active TB remains limited, even with newer antigens encoded in the RD-1 region of Mycobacterium tuberculosis.

Adolescent↗
PubMed2003

Modified de Gramont with oxaliplatin in the first-line treatment of advanced colorectal cancer.

We previously reported high activity for oxaliplatin and a modified de Gramont regimen (OxMdG) in a single centre study of patients with metastatic colorectal cancer. We now report results with a further 56 patients treated at 14 centres. Low rates of grade 3 and 4 toxicity were seen, with no toxic deaths. Objective response rates were CR/PR=53%; NC=34.7%; PD=12.2%. Median time to progression was 8.3 months and overall survival was 14.5 months. This regimen is more convenient than those based around the conventional de Gramont regimen but is highly active and well tolerated; it forms part of a current UK MRC phase 3 trial.

Adult↗
PubMed2002

Investigation of environmental and host-related risk factors for tuberculosis in Africa. I. Methodological aspects of a combined design.

Host-related and environmental factors for tuberculosis have usually been investigated separately using different study designs. Joint investigation of the genetic, immunologic, and environmental factors at play in susceptibility to tuberculosis represents an innovative goal for obtaining a better understanding of the pathogenesis of the disease. In this paper, the authors describe methods being used to investigate these points in a West African study combining several designs. Patients with newly diagnosed smear-positive cases of tuberculosis are recruited. The effect of host-related factors is assessed by comparing each case with a healthy control from the case's household. The role of environmental factors is estimated by comparing cases with randomly selected community controls. The frequencies of candidate gene variants are compared between cases and community controls, and results are validated through family-based association studies. Members of the households of cases and community controls are being followed prospectively to determine the incidence of "secondary" tuberculosis and to evaluate the influence of geographic and genetic proximity to the index case. This type of design raises important methodological issues that may be useful to consider in studies investigating the natural history of infectious diseases and in attempts to disentangle the effects of environmental and genetic factors in response to infection.

Africa, Western↗
PubMed2002

Investigation of environmental and host-related risk factors for tuberculosis in Africa. II. Investigation of host genetic factors.

In an accompanying paper (Am. J. Epidemiol. 2002;155:1066-73), the authors describe the design of a large multicenter study being carried out in three West African countries for investigation of the roles of environmental and host-related factors in the development of tuberculosis. In this paper, the authors review some evidence that host genetic factors play a role in susceptibility to tuberculosis. They describe the three components of the study that are designed to investigate the effect of host genetic factors on the development of tuberculosis: case-control and family-based association studies of candidate genes and analysis of affected relative pairs to screen the human genome for areas of linkage to the disease. The authors also address a number of methodological issues that arise, such as the effects of consanguinity, half-siblings, and nonpaternity. Lastly, they review opportunities to assess gene-environment interaction in the framework of the study, in light of current methodological knowledge. Consideration of these issues may be useful in the design of other studies of genetic susceptibility to infectious diseases, particularly those to be carried out in developing countries.

Africa, Western↗
PubMed2001

Improvement in quality of life for cancer patients treated with epoetin alfa.

Anaemia is a common complication of cancer and cancer therapies, and fatigue is one of the most common symptoms of anaemia, disrupting functional performance and reducing overall quality of life. The positive effects of treating renal patients with recombinant human erythropoietin are well documented. This case report series details the specific effects of fatigue on individual patients with cancer and their way of life, and describes their significant improvement in lifestyle following the reversal of anaemia using recombinant human erythropoietin, epoetin alfa.

Aged↗
PubMed2001

Prevalence of herpes simplex type 2 and syphilis serology among young adults in a rural Gambian community.

OBJECTIVES: To estimate prevalence and risk factors for herpes simplex 2 (HSV2) positivity, syphilis and Chlamydia trachomatis infection among rural people aged 15-34 in the Gambia. METHODS: Questionnaires and serum samples were collected from 1076 men and women aged 15-34 during a cross sectional prevalence survey in a rural area of the Gambia. Sera were screened for antibodies to herpes simplex virus type 2 (HSV2), and for syphilis using Treponema pallidum haemagglutination assay (TPHA) and rapid plasma reagin (RPR) tests. Urine was tested by polymerase chain reaction (PCR) for C trachomatis infection. RESULTS: 28% of women and 5% of men were HSV2 ELISA positive; 10% of women and 2% of men were TPHA positive; and 7% of women and 1% of men were both RPR and TPHA positive. Out of 1030 urine sample tested only six were positive for C trachomatis. 7% of those who reported never having sex were positive for one or other of these tests. Prevalences of all STIs increased with age and were higher in women than men. Women were much less likely than men to seek treatment for STI symptoms at a health centre. Married people were at increased risk of an STI compared with single people. Jola and Fula women had a higher prevalence of HSV2 than women from other ethnic groups, and Fulas also had a higher prevalence of RPR/TPHA positivity. The limited number of sexual behaviour questions were not significantly associated with STIs after adjustment for age, marital status, and ethnic group. CONCLUSIONS: The prevalences of the ulcerative infections HSV2 and syphilis in this population are a cause for concern. In a setting where HIV1 prevalence remains low this indicates an urgent need for STI control and behaviour change programmes to prevent an HIV epidemic. Concerns about the validity of reported sexual behaviour data high light the necessity of biological markers in the evaluation of behaviour change programmes.

Adolescent↗
PubMed2001

Management of sexually transmitted diseases in urban pharmacies in The Gambia.

This study aimed to describe the quality and costs of sexually transmitted disease (STD) case management in urban pharmacies in The Gambia, and explore pharmacy workers' (PWs) willingness to improve the STD care they provide. PWs from 24 registered pharmacies were interviewed in order to collect information on their knowledge and practices regarding management of STDs. The same pharmacies were visited by a male 'simulated client' (SC) to ascertain how urethral discharge syndrome (UDS) cases were managed in practice. Fifteen (63%) pharmacies were equipped for treatment of UDS, pelvic inflammatory disease (PID) and genital ulcer syndrome (GUS), according to national guidelines. Appropriate syndromic management for UDS was mentioned by 11% of PWs but actually given to 4.4% of the SC visits. None of the PID or GUS cases would be treated correctly. Forty-two per cent of PWs advised on partner notification, 38% on safe sex and 29% on treatment compliance in the SC visits. The reported costs for treatment of UDS, PID and GUS ranged from $2.5-$15.0. The cost of treatment actually purchased by the SC averaged $3.5 (range $1.5-$9.6) for UDS. Excluding the pharmacy sector from interventions will limit the impact of STD control measures. Regular training in syndromic management and rational drug use, with a concise manual for reference are recommended. Strategies to lower the cost of drugs should be explored.

Adult↗
PubMed2000

Efficacy of artesunate plus pyrimethamine-sulphadoxine for uncomplicated malaria in Gambian children: a double-blind, randomised, controlled trial.

BACKGROUND: Resistance to cheap effective antimalarial drugs, especially to pyrimethaminesulphadoxine (Fansidar), is likely to have a striking impact on childhood mortality in sub-Sharan Africa. The use of artesunate (artesunic acid) [corrected] in combination with pyrimethamine-sulphadoxine may delay or prevent resistance. We investigated the efficacy, safety, and tolerability of this combined treatment. METHODS: We did a double-blind, randomised, placebo-controlled trial in The Gambia. 600 children with acute uncomplicated Plasmodium falciparum malaria, aged 6 months to 10 years, at five health centres were randomly assigned pyrimethaminesulphadoxine (25 mg/500 mg) with placebo; pyrimethamine-sulphadoxine plus one dose of artesunate (4mg/kg bodyweight); or pyrimethamine-sulphadoxine plus one dose 4 mg/kg bodyweight artesunate daily for 3 days. Children were visited at home each day after the start of treatment until parasitaemia had cleared. FINDINGS: The combined treatment was well tolerated. No adverse reactions attributable to treatment were recorded. By day 1, only 178 (47%) of 381 children treated with artesunate were still parasitaemic, compared with 157 (81%) of 195 children in the pyrimethamine-sulphadoxine alone group (relative risk 1.7 [95% CI 1.5-2.0], p<0.001). Treatment-failure rates at day 14 were 3.1% in the pyrimethamine sulphadoxine alone group, and 3.7% in the one-dose artesunate group (risk difference -0.6% [-4.2 to 3.0]) and 1.6% in the three-dose group (1.5 [1.5-4.5], p=0.048). Symptoms resolved faster in children who received artesunate, but there was no additional benefit for three doses of artesunate over one dose. Children given artesunate were less likely to be gametocytaemic after treatment. INTERPRETATION: The combined treatment was safe, well tolerated, and effective. The addition of artesunate to malaria treatment regimens in Africa results in lower gametocyte rates and may lower transmission rates.

Animals↗
PubMed1998

A randomized controlled trial of artemether/benflumetol, a new antimalarial and pyrimethamine/sulfadoxine in the treatment of uncomplicated falciparum malaria in African children.

We report here the results of a randomized double blind trial comparing coartemether (CGP56697), a combination of artemether and benflumetol, with pyrimethamine/sulfadoxine (P/S). Two hundred eighty-seven children 1-5 years of age with uncomplicated falciparum malaria were enrolled at two centers in The Gambia between July 1996 and December 1996. Following treatment, children were visited at home every 24 hr until a blood film free of asexual parasites was obtained. Genotyping of parasites was used to distinguish recrudescence from new infections. Three days after the start of treatment, 133 (100%) of the CGP56697-treated children compared with 128 (93.4%) of children treated with P/S had cleared their parasites (P = 0.003). The day 15 cure rate was 93.3% for CGP56697 and 97.7% for P/S (P = 0.13). Within the third and fourth week after initiation of therapy, 20 children treated with CGP56697 and one of the P/S-treated children returned with second malaria episodes (P < 0.0001). Genotyping suggested that the majority (19 of 23 [82.6%]) of these second episodes were due to new infections, supporting the World Health Organization recommendation that longer follow-up is not relevant for the assessment of drug efficacy. At the two-week follow-up, 28.9% of the P/S treated children but none of the CGP56697-treated children carried gametocytes (P < 0.0001). This study showed that CGP56697 is safe in African children with acute uncomplicated falciparum malaria, clears parasites more rapidly than P/S, and results in fewer gametocyte carriers. More frequent new infections within the third and fourth week following treatment with CGP56697 than treatment with P/S are likely to be due to the short prophylactic effect of CGP56697.

Antimalarials↗
PubMed1995

THP-1 macrophage membrane-bound plasmin activity is up-regulated by transforming growth factor-beta 1 via increased expression of urokinase and the urokinase receptor.

Receptors for urokinase (uPA) and plasminogen provide a mechanism to direct the cellular activation of plasminogen. The regulation of these receptors is important for several macrophage functions. In these studies, the effect of transforming growth factor-beta 1 (TGF-beta 1) on uPA, uPA receptor, and plasminogen receptor expression by human THP-1 macrophage was examined. TGF-beta 1 induction of uPA expression by THP-1 cells was differentiation dependent. Suspension and adherent cultures expressed similar constitutive levels of uPA. Exposure of adherent cells to TGF-beta 1 led to a dose- and time-dependent increase in uPA activity which was paralleled by an increase in uPA antigen and uPA mRNA. In contrast, uPA expression by suspension cultures was unresponsive to TGF-beta 1. The differential response exhibited by suspension and adherent THP-1 cells may reflect differences in their expression of TGF-beta 1 receptors, since when assayed by crosslinking techniques, suspension cells primarily expressed a 65 kDa receptor; whereas, the adherent cells expressed 65 and 100 kDa receptors. TGF-beta 1-induced alterations in uPA receptor expression by adherent THP-1 cells were examined by quantitating membrane-bound uPA activity. Membrane-bound uPA activity increased three-fold when cells were incubated with TGF-beta 1. The increase in membrane-uPA activity expressed by TGF-beta 1-treated cells was not due to increased uPA receptor occupancy since incubation of either control or TGF-beta 1 primed cells with exogenous uPA did not lead to an increase in membrane-bound uPA activity. Furthermore, immunoreactive uPA receptor was increased in TGF-beta 1-treated cells. Following incubation with plasminogen, membrane-bound plasmin activity increased three-fold in TGF-beta 1-treated cells. However, no change in immunoreactive membrane-bound plasmin(ogen) was observed. In addition, binding of 125I-Lys-plasminogen to THP-1 cells was not affected by TGF-beta 1 treatment. We conclude that TGF-beta 1 stimulates membrane-bound plasmin activity, without affecting plasminogen receptor expression, through the up-regulation of uPA and the uPA receptor expression.

Cell Adhesion↗
PubMed1994

Regulation of macrophage receptor-bound plasmin by autoproteolysis.

The activation of plasminogen by macrophage is regulated by their expression of receptors for urokinase and plasmin(ogen). In these studies we have examined plasmin(ogen) binding to adherent human THP-1 macrophage. Plasmin bound to the THP-1 cells in a time- and dose-dependent manner (Kd 15.8 +/- 6.2 nM; Bmax 1.4 +/- 0.3 x 10(6)/cell). The lysine analog epsilon-aminocaproic acid competitively inhibited plasmin binding. The fraction of membrane-bound plasmin, however, became increasingly resistant to displacement with epsilon-aminocaproic acid. Over a 24-h period, membrane-bound plasmin activity fell 80% despite the presence of catalytically active plasmin in the incubation media. The loss of receptor-bound plasmin activity was not due to proteolytic alterations of its receptor since 125I-Lys-plasminogen bound to THP-1 cells pretreated with plasmin with similar affinity as to untreated cells. Following a 24-h incubation of 125I-Lys-plasminogen or 125I-plasmin with THP-1 cells, several degradative fragments were apparent in their conditioned media. The smaller degradative fragments (28 and 36 kDa) lacked cell binding activity and were demonstrated to be active by casein-zymography. A 48-kDa fragment bound to cells in a lysine-dependent manner but was not active. In contrast, phenylmethylsulfonyl fluoride-inactivated 125I-plasmin retained its binding activity over 24 h, and degradative fragments were not present in the conditioned media. The binding of 125I-Lys-plasmin(ogen) to THP-1 cells was also examined in the presence of excess alpha 2 plasmin inhibitor. Despite the absence of fluid-phase plasmin activity, membrane-bound 125I-Lys-plasmin(ogen) decreased over 24 h. At 24 h a radiolabeled 48-kDa fragment was observed in the conditioned media and together with 125I-Lys-plasmin(ogen) was bound to cells. Unlike 125I-Lys-plasmin, the 48-kDa fragment did not form a complex with alpha 2 plasmin inhibitor. Thus, autoproteolysis of receptor-bound plasmin results in fragments with truncated physiologic properties that possess either cell binding or catalytic activities. We propose that autoproteolysis is a mechanism for regulating membrane-bound plasmin activity.

Catalysis↗
PubMed1993

The impact of HIV on resource utilization by patients with tuberculosis in a tertiary referral hospital, Nairobi, Kenya.

By using routinely collected data and results from research studies at the Infectious Diseases Hospital (IDH), Nairobi, we have begun to determine the scale of the increase in resource utilisation and treatment costs for tuberculosis control services caused by the HIV epidemic. New cases of tuberculosis registered annually at the IDH rose 61%, from 447 in 1985 to 720 in 1990. HIV seroprevalence among patients with tuberculosis rose from 7.5% in 1986 to 42% in 1990. The inpatient mortality rate rose from 8.4% in 1985 to 16.8% in 1989, but fell to 13.5% in 1990. HIV-positive patients were admitted to hospital on 2 or more occasions more often than HIV-negative patients (Relative risk (RR) = 2.46, 95% confidence intervals (CI), 1.1-5.7), but average duration of admission was similar for the 2 groups. Significantly more HIV-positive patients were prescribed antibiotics, antifungal agents, antidiarrhoeal agents, analgesics and corticosteroids than HIV-negative patients. Microbiological investigations, apart from those for tuberculosis, were performed more commonly among HIV-positive patients (RR = 2.0, 95% CI 1.0-4.2). Using this data, the average cost of ideal drug therapy, including antituberculosis drugs and treatment for intercurrent infections and other complications, was estimated using 1992 prices (ECHO, Coulsdon Surrey, UK). The costs were US$16.62 and US$32.94 for HIV-negative patients using 'standard' therapy (2STH/10TH) and short course therapy (2SHRZ/6TH) respectively, and US$41.18 for HIV-positive patients using a short-course regimen without thiacetazone (2EHRZ/6EH). The HIV epidemic is causing both an increase in the numbers of patients requiring treatment and an increase in the average cost of treatment per patients.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1992

Cohort study of human immunodeficiency virus infection in patients with tuberculosis in Nairobi, Kenya. Analysis of early (6-month) mortality.

Retrospective studies suggest that the mortality rate from HIV-1-associated tuberculosis is greater than that from tuberculosis alone, but it is not clear if this is due to failure of antituberculosis treatment or to the complications of HIV-1 infection. We have carried out a prospective cohort study of patients with tuberculosis in Nairobi, Kenya, to compare mortality rates, risk factors, and causes of death in HIV-1 positive and HIV-1 negative patients. One hundred seven HIV-1 positive and 174 HIV-1 negative patients with tuberculosis attending two tuberculosis treatment centers in Nairobi were enrolled and followed monthly. Mortality was significantly higher in HIV-1 positive than in HIV-1 negative patients within 6 months of the start of antituberculosis treatment after adjustment for age, sex, and education (rate ratio = 3.8; 95% confidence interval, 1.7 to 8.1; p less than 0.001). Most of the excess mortality occurred after the first month of treatment and was due to nontuberculous infections. Predictors for mortality differed greatly between HIV-1 positive and HIV-1 negative patients. Mortality was greater in HIV-1 positive patients treated with a "standard" regimen for tuberculosis than in HIV-1 positive patients receiving a "short-course" regimen (p = 0.08 when adjusted for all independent risk factors). Tuberculosis control programs in developing countries need to implement "short-course" regimens and train health workers to recognize and treat nontuberculous infections to maintain their effectiveness in the face of the HIV epidemic.

AIDS-Related Opportunistic Infections↗
PubMed1990

Determining nursing retention strategy in a large public teaching hospital.

In 1988, the Los Angeles County University of Southern California Medical Center (LAC USC) surveyed 1,102 RNs (75% of its total RN population) to determine factors critical to nursing retention. The Nursing Retention Survey required participants to rank 46 retention factors related to compensation benefits, work environment, amount and type of work, work relationships, availability of support services, management practices, and opportunities for professional growth. This article reports survey responses for the ten most significant and ten least significant retention factors. Survey findings, which guided LAC USC in designing nursing retention strategies, show that RNs who stated that they would leave their jobs were consistently less satisfied with all the top-ranking important elements than those who would stay.

Attitude of Health Personnel↗