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Biomedical subjects

R Waddell

Publications and source records attributed to R Waddell.

15 recordsLinked to original sources

The effect of nitrostyrene on cell proliferation and macrophage immune responses.

The use of mood enhancing drugs such as amphetamine and ecstasy are now prevalent in society. These compounds are known to produce serious psychological and physiological problems in users, which can, in some circumstances result in death. While there has been much research into the effects of these drugs on the body, little if any research has investigated the effect of the side products and synthetic reaction by-products which are a consequence of there illegal production. In the study the effects of nitrostyrene, a reaction by-product in one of the routes to synthesis of amphetamine sulphate, on cell viability and macrophage function was determined. Treatment with nitrostyrene at doses >0.75 microg/mL had a significant suppressive effect on the proliferation of stomach cancer lines. Treatment of macrophages with doses as high as 10 microg/mL did not effect cell viability. Nitrostyrene treatment of macrophages, stimulated with IFN gamma and LPS, resulted in a dose dependent differential inhibition in IL12, IL6 and nitrite production, even using doses < 0.5 microg/mL. Thus ranking of the three, on the basis of the suppressive effect obtained, is IL12 > nitrite > IL6. Thus ingestion of nitrostyrene contaminated ecstasy is likely to have a adverse effect on the immune responses of the recreational user.

Amphetamine-Related Disorders↗

Time trends in HIV incidence among homosexually active men seen at sexual health clinics in Australia, 1993-1999.

BACKGROUND: Increases in sexual risk behaviour have recently been reported among homosexually active men in Australia and in other industrialised countries, potentially facilitating an increase in HIV incidence. OBJECTIVE: To monitor HIV incidence among homosexually active men seen through a network of sexual health clinics in Australia. STUDY DESIGN: Selected metropolitan public sexual health clinics provided counts of the number of people seen at the clinics during a calendar year, the number voluntarily tested for HIV antibody and the number newly diagnosed with HIV infection, broken down by sex, age group, HIV exposure category and HIV antibody testing history. HIV incidence was estimated among homosexually active men with a history of a negative test in the 12 months prior to last being seen in a calendar year. RESULTS: Of 23924 men seen at the clinics in 1993-1999 with a reported history of male homosexual contact, 7440 (31.1%) had a negative test in the 12 months prior to last being seen in a calendar year. The percentage of men with a recent negative test declined significantly over time, from more than 33% in 1994-1996 to 29% in 1999 (P=0.003), and with increasing age, from 34.3% among men aged 25-29 years to 27.4% among men aged 40 years or older (P<0.0005). A total of 5346 (71.9%) men were retested for HIV antibody within 12 months of the last negative test. The percentage of men retested declined significantly over time, from 77.8% in 1994 to 67.2% in 1999 (P=0.021) but did not change by age group (P=0.132). Overall, 56 men were newly diagnosed with HIV infection. Estimated HIV incidence was 2.1% in 1993-1999; incidence did not change significantly by year (P=0.498) or age group (P=0.757). CONCLUSION: HIV incidence has remained stable among homosexually active men seen through a network of sexual health clinics in Australia.

Adolescent↗

Skin test reactions to Mycobacterium tuberculosis purified protein derivative and Mycobacterium avium sensitin among health care workers and medical students in the United States.

SETTING: Health care workers and medical students in the United States subject to annual tuberculin skin testing. OBJECTIVE: To use skin testing with Mycobacterium avium sensitin (MAS) to determine contemporary rates of infection with non-tuberculous mycobacteria (NTM) and their effect on reactions to M. tuberculosis purified protein derivative (PPD). DESIGN: Dual skin testing was performed with PPD and MAS on 784 health care workers and medical students in the northern and southern US. MAS reactions that were > or = 5 mm and also > or = 3 mm larger than the PPD reaction were defined as MAS dominant and due to NTM. RESULTS: MAS reactions were > or = 5 mm in 40% and > or = 15 mm in 18% of subjects; 95% were MAS dominant. MAS dominant reactions were more common in the south than the north (P < 0.001). PPD reactions were > or = 15 mm in 3% of subjects. PPD reactions > or = 15 mm were more common among males, foreign born subjects and subjects with BCG immunization (all P < 0.001). MAS dominant reactions were found in 82% of subjects with 5-9 mm PPD reactions and 50% with 10-14 mm PPD reactions; these reactions were more common among whites (P = 0.046), US-born (P = 0.038) and subjects without BCG immunization (P = 0.004). CONCLUSIONS: Infections with NTM are responsible for the majority of 5-14 mm PPD reactions among US-born health care workers and medical students subject to annual tuberculin testing.

Adult↗

High rates of disseminated infection due to non-tuberculous mycobacteria among AIDS patients in Finland.

OBJECTIVE: to determine the rate of disseminated infection due to non-tuberculous mycobacteria (NTM) among Finnish AIDS patients, and to analyse the epidemiology of these infections. METHODS: in a prospective cohort study HIV-infected patients with CD4 counts < 200 x 10(6)/l were interviewed, and had mycobacterial blood cultures performed at baseline and at 6 months, then subsequently for clinical indications; autopsies were performed on patients who died. The cohort was followed at least for 24 months or to death. Water samples were collected from the homes of patients and from the environment and cultured for organisms of the Myobacterium avium complex (MAC). Environmental and clinical isolates were compared using pulsed field gel electrophoresis (PFGE). RESULTS: NTM infection occurred in 22 (43%) of 51, 19 isolates were Mycobacterium avium, two M. genavense and one M. intracellulare. Multivariate analysis identified urban residence (P=0.04) and eating raw fish (P=0.04) as independent risk factors. Molecular analysis revealed two clusters of related isolates (three M. avium, two M. genavense) among urban residents. CONCLUSION: AIDS patients in Finland have high rates of disseminated infection due to NTM. Clusters of identical organisms and association with urban residence suggests that these are newly acquired infections in advanced AIDS.

AIDS-Related Opportunistic Infections↗

Cellular immune responses to mycobacteria in healthy and human immunodeficiency virus-positive subjects in the United States after a five-dose schedule of Mycobacterium vaccae vaccine.

The safety and immunogenicity of heat-killed Mycobacterium vaccae vaccine were investigated in a pilot study assessing the feasibility of immunization to prevent mycobacterial disease in patients with human immunodeficiency virus (HIV) infection. Fifteen (seven healthy and eight HIV-positive subjects) received five doses of M. vaccae vaccine. Lymphocyte proliferation assays (LPAs) were performed using Mycobacterium avium sensitin (MAS) and M. vaccae sonicate (MVS). Vaccine was well tolerated in all 15 subjects with minimal induration at the vaccine site. LPAs for four of seven healthy vaccines were positive for MAS after immunization. Median responses to MAS and MVS that were determined by LPAs were consistently higher for the eight HIV-positive vaccinees than for the seven healthy controls. A five-dose series of M. vaccae vaccine is safe for both healthy and HIV-positive subjects and deserves further evaluation as a vaccine to prevent HIV-associated mycobacterial disease.

Bacterial Vaccines↗

A prolonged outbreak of Campylobacter infection at a training facility.

Campylobacter outbreaks are rarely detected despite Campylobacter being the most common food-borne illness notified to public health authorities. We report a prolonged outbreak of Campylobacter occurring over a three month period at a training facility. Seventy-eight cases were detected, 16 of which were confirmed Campylobacter infections. In seven affected groups of people using the facility, the attack rate ranged between 19% and 67%. An investigation of one sporting group showed that illness was associated with consumption of cucumber served at a self-serve salad bar. Six people attending the facility in other weeks also reported illness after eating only at the salad bar. Transmission of Campylobacter ceased after changes were instituted to food preparation and storage in the facility kitchen.

Adolescent↗

The risks and benefits of childhood bacille Calmette-Guérin immunization among adults with AIDS. International MAC study groups.

OBJECTIVE: To define the risks of disseminated bacille Calmette-Guérin (BCG) or disseminated Mycobacterium tuberculosis in adults with AIDS who were immunized with BCG in childhood. DESIGN: HIV-infected patients with CD4 < 200 x 10(6)/l were enrolled from five study sites (New Hampshire, Boston, Finland, Trinidad and Kenya). Prior BCG immunization was determined and blood cultures for mycobacteria were obtained at study entry and at 6 months. Acid-fast bacilli were identified as Mycobacterium tuberculosis complex (MTBC) using DNA probes. MTBC isolates were then typed by both IS6110 restriction fragment length polymorphism and polymerase chain reaction/restriction enzyme analysis. SETTING: Most patients in New Hampshire and Finland were outpatients; most patients in Trinidad were inpatients with terminal illness; and most patients in Kenya were outpatients, although 44 were inpatients with terminal illness. PARTICIPANTS: A total of 566 patients were enrolled, including 155 with childhood BCG immunization; 318 patients had a single study visit and culture, and 248 patients had two study visits and cultures. MAIN OUTCOME MEASURES: Isolation and identification of mycobacteria from blood cultures. RESULTS: Blood cultures were positive for MTBC in 21 patients; none were positive for M. bovis BCG, and 21 were M. tuberculosis-positive. In Trinidad, seven (87%) out of eight isolates of M. tuberculosis were indistinguishable by IS6110 typing; BCG immunization was associated with a decreased risk of bacteremic infection with M. tuberculosis (P = 0.05). CONCLUSIONS: The risk of disseminated BCG among adult AIDS patients with childhood BCG immunization is very low. Childhood BCG immunization is associated with protection against bacteremia with M. tuberculosis among adults with advanced AIDS in Trinidad.

AIDS-Related Opportunistic Infections↗

Detection of Chlamydia trachomatis in urine samples by nucleic acid tests: comparison with culture and enzyme immunoassay of genital swab specimens.

Two commercially available nucleic acid-based tests, ligase chain reaction (LCR; Abbott Laboratories) and PCR (Roche Diagnostics), for the detection of Chlamydia trachomatis in male and female urine samples were compared with culture and enzyme immunoassay (EIA) (Microtrak; Syva) for C. trachomatis detection in genital samples. The samples were collected from 1,005 patients who attended a sexually transmitted disease clinic. In this study population, the prevalence of the infection was 4%. Specimens which were reactive in any of the tests were retested with a different PCR test using primers directed against the major outer membrane protein gene. With a "gold standard" of a positive culture, or any other positive test result if it was confirmed by an independent test, the Roche PCR (95% sensitive, 99.9% specific) was more sensitive than the LCR (75% sensitive, 100% specific) (chi2, P < 0.0001) while both tests were more sensitive than culture (58% sensitive, 100% specific) or EIA (45% sensitive, 100% specific) (chi2, P < 0.001). The Roche PCR and Abbott LCR tests of urine identified 65% and 30% more positive patients, respectively, than did testing by culture of urethral or cervical specimens. Nucleic acid testing of urine specimens for C. trachomatis is a more sensitive and convenient method for the detection of genital infection.

Bacteriological Techniques↗

The international epidemiology of disseminated Mycobacterium avium complex infection in AIDS. International MAC Study Group.

OBJECTIVE: To determine rates of disseminated Mycobacterium avium complex (MAC) infection among AIDS patients in developed and developing countries, and to determine whether different rates reflect differences in exposure or immunity, or both. DESIGN: Prospective cohort study. SETTING: University hospitals and outpatient AIDS programs. METHODS: HIV-infected subjects with CD4 counts < 200 x 10(6)/l were interviewed and had CD4 lymphocyte counts, blood cultures for mycobacteria (baseline and at 6 months), and skin tests with purified protein derivative (PPD) and M. avium sensitin. RESULTS: Among 566 study patients rates of disseminated MAC were 10.5-21.6% in New Hampshire, Boston and Finland compared to 2.4-2.6% in Trinidad and Kenya (P < 0.001). PPD skin test reactions > or = 5 mm were present in 20% of patients from Kenya compared to 1% at other sites (P < 0.001). Among patients from the United States and Finland, multiple logistic regression indicated that occupational exposure to soil and water was associated with a decreased risk of disseminated MAC, whereas the following were associated with an increased risk of disseminated MAC: low CD4 count, swimming in an indoor pool, history of bronchoscopy, regular consumption of raw or partially cooked fish/shellfish and treatment with granulocyte colony-stimulating factor. CONCLUSIONS: Rates of disseminated MAC in AIDS are higher in developed than developing countries and are due to both differences in exposure and differences in immunity. These data provide a rationale for prevention of MAC through both active immunization and reduction in exposure to the organism.

AIDS-Related Opportunistic Infections↗

Incontinence aids in perspective.

Social continence is achieved through successful use of incontinence aids, which should only be considered after a thorough investigation. They may be used temporarily in conjunction with treatment or long term. The authors provide a brief overview of aids commonly used in the management of urinary incontinence and suggest ways of assisting the individual or carer to make the correct choice.

Clothing↗

Activation of carbamoyl phosphate synthase by N-acetyl-L-aspartate.

Carbamoyl phosphate synthase from liver of both rat and frog, normally dependent on N-acetyl-l-glutamate (on the basis of K(m) and physiological concentrations) as an activator, was shown to be activated by high concentrations of N-acetyl-l-aspartate. However, the high concentrations of N-acetyl-l-aspartate required for activation produce non-competitive inhibition. Similarly, high concentrations of N-acetyl-l-glutamate, in very large excess of the amount required to activate the enzyme, inhibit. The limit for N-acetyl-l-glutamate as an impurity in N-acetyl-l-aspartate was found to be less than 1 in 5000 parts, far below the 1 in 250 parts needed to produce the activation observed with N-acetyl-l-aspartate.

Animals↗