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Biomedical subjects

R Brindle

Publications and source records attributed to R Brindle.

At least 19 recordsLinked to original sources
PubMed2001

Serial counts of Mycobacterium tuberculosis in sputum as surrogate markers of the sterilising activity of rifampicin and pyrazinamide in treating pulmonary tuberculosis.

BACKGROUND: Since the sterilising activity of new antituberculosis drugs is difficult to assess by conventional phase III studies, surrogate methods related to eventual relapse rates are required. METHODS: A suitable method is suggested by a retrospective analysis of viable counts of Mycobacterium tuberculosis in 12-hr sputum collections from 122 newly diagnosed patients with pulmonary tuberculosis in Nairobi, done pretreatment and at 2, 7, 14 and 28 days. Treatment was with isoniazid and streptomycin, supplemented with either thiacetazone (SHT) or rifampicin + pyrazinamide (SHRZ). RESULTS: During days 0-2, a large kill due to isoniazid occurred, unrelated to treatment or HIV status; thereafter it decreased exponentially. SHRZ appeared to have greater sterilising activity than SHT during days 2-7 (p = 0.044), due to rifampicin, and during days 14-28, probably due mainly to pyrazinamide. The greatest discrimination between SHRZ and SHT treatments was found between regression estimates of kill over days 2-28 (p = 0.0005) in patients who remained positive up to 28 days with homogeneous kill rates. No associations were found between regression estimates and the age, sex, and extent of disease or cavitation. An increased kill in HIV seropositive patients, unrelated to the treatment effect, was evident during days 2-28 (p = 0.007), mainly during days 2-7. CONCLUSIONS: Surrogate marker studies should either be in small groups treated with monotherapy during days 2 to about 7 or as add-ons or replacements in isoniazid-containing standard regimens from days 2 to 28 in large groups.

Journal Article↗
PubMed2000

Oral health in Hlabisa, KwaZulu/Natal--a rural school and community based survey.

AIMS: To investigate rates of dental caries and periodontal disease, available dental services and resources and perceived needs in a rural South African community. DESIGN: A cross-sectional field study including situational analysis and focus group discussions. SETTING: KwaZulu/Natal, South Africa. PARTICIPANTS: A total of 520 children, adolescents and adults. METHODS: WHO caries scores and periodontal CPI score were determined through clinical examinations in five age groups, 5-6 years, 12 y, 15 y, 35-54 y, 55 y+. Focus groups included ten 15-year-old children and ten adults. RESULTS: Caries prevalences and (mean scores) were 5-6 y 64% (dmft 3.0), 12 y 24% (DMFT 0.4), 15 y 27% (DMFT 0.8), 35-54 69% (DFT 2.6) and 55 y+ 80% (DFT 2.7). Most caries was untreated and where present, treatment had been extraction. Dental caries rates were low and except for 5-6 y were within WHO targets for the year 2000. Periodontal disease prevalence was high but would respond to improved oral hygiene. Knowledge of oral health was rudimentary. CONCLUSIONS: A district-wide oral health promotion programme is required preceded by research to define effective health education messages. Access to simple but effective preventive and curative services would seem reasonable. In view of the lack of resources ART is suggested as caries treatment.

Adolescent↗
PubMed1999

n-Alkyl fluorenyl phases in chromatography. II. Dynamic behavior and high-performance liquid chromatography applications.

The dynamic behavior of two n-hexyl fluorenyl phases (fluorene-6A [3a(Tn)(Qm)y], fluorene-6B [3b(Tn)(Qm)y]) and three n-decyl fluorenyl phases (fluorene-10A [4a(Tn)(Qm)y], fluorene-10B [4b(Tn)(Qm)y], and fluorene-10C [4c(M1)(Qm)y]) is investigated by solid-state nuclear magnetic resonance (NMR) spectroscopy using the dipolar filter technique with both 13C and 1H detection. These results are compared with those from other dynamic measurements, like the relaxation times in the rotating frame (T1pH) and the variation of the contact time (T(CH)). Additionally, another type of a fluorenyl phase [5a(Tn)(Qm)y], which has an aromatic moiety connected to the silica gel by amido couplings, was also investigated by the dipolar filter method. The solid-state NMR dynamic measurements indicate an increased mobility of the n-alkyl fluorenyl phases compared to the amido coupled fluorenyl phase. The lower the ligand density of the studied n-alkyl fluorenyl phases, the higher their mobility. The separation behavior of the respective phases in high-performance liquid chromatography was investigated with samples containing polycyclic aromatic hydrocarbons and nitro explosives. Depending on the amount of the chemically bound aromatic moiety and the length of their n-alkyl spacer groups, pi-pi interactions with the solute molecules are involved in the separation process and cause it to proceed at a different rate. Therefore, n-alkyl fluorenyl phases can be classified as mixed-mode phases.

Chromatography, High Pressure Liquid↗
PubMed1999

Role for tumor necrosis factor alpha receptor 1 and interleukin-1 receptor in the suppression of mouse hepatocyte apoptosis by the peroxisome proliferator nafenopin.

Peroxisome proliferators (PPs) cause rodent liver enlargement and tumors. In vitro, PPs induce rat and mouse hepatocyte DNA synthesis and suppress apoptosis, a response mimicked by exogenous tumor necrosis factor alpha (TNFalpha). Here, we determine the role of TNF receptor 1 (TNFR1), TNF receptor 2 (TNFR2), and nuclear factor kappa beta (NFkappaB) in the response of mouse hepatocytes to the PP, nafenopin. Nafenopin (50 micromol/L) induced DNA synthesis as measured by bromodeoxyuridine (BrdU) incorporation, suppressed cell death as measured by Hoechst 33258 staining, induced peroxisomal beta-oxidation as measured by cyanide insensitive palmitoyl CoA oxidation (PCO) and caused activation of nuclear factor kappa beta (NFkappaB) as determined by electrophoretic mobility gel shift assay (EMSA). The induction of DNA synthesis and the suppression of apoptosis in response to nafenopin was abrogated completely by blocking antibodies to TNFR1 but not to TNFR2. In contrast, the induction of peroxisomal beta-oxidation by nafenopin was not blocked by the anti-TNFR1 antibody. Next, we evaluated the response of hepatocytes to interleukin-1 (IL-1), another proinflammatory cytokine. IL-1alpha (2.5 ng/mL) and, to a lesser extent, IL-1beta (5 ng/mL), shared the ability of TNFalpha to induce DNA synthesis and suppress apoptosis. In addition, anti-IL-1 receptor, type 1/p80 (IL-1R) antibodies were able to abrogate the response to nafenopin. IL-1alpha was still able to perturb hepatocyte growth in the presence of the anti-TNFR1 antibody suggesting that IL-1alpha acts independently rather than by elaborating TNFalpha. In summary, these data provide additional evidence for a role for hepatic cytokines in the perturbation of hepatocyte growth by PPs such as nafenopin.

Animals↗
PubMed1998

Peroxisome proliferator-activated receptor (PPAR) alpha-regulated growth responses and their importance to hepatocarcinogenesis.

Peroxisome proliferators (PPs) are a class of non-genotoxic rodent hepatocarcinogens that act by perturbing liver growth regulation. We have demonstrated previously that PPs suppress both spontaneous rat hepatocyte apoptosis and that induced by exogenous stimuli such as transforming growth factor-beta1 (TGF beta1). More recently, we have demonstrated that PPs can suppress apoptosis induced by more diverse stimuli such as DNA damage or ligation of Fas, a receptor related to the tumour necrosis factor alpha (TNF alpha) family of cell surface receptors. PPs transcriptionally activate the peroxisome proliferator activated receptor-alpha, PPAR alpha, a member of the nuclear hormone receptor superfamily. We investigated whether activation of PPAR alpha mediates the suppression of rat hepatocyte apoptosis induced by PPs. We isolated a naturally occurring variant form of PPAR alpha (hPPAR alpha-6/29) from human liver by PCR cloning. hPPAR alpha-6/29 shared the ability of mPPAR alpha to bind to DNA but, unlike mPPAR alpha, could not be activated by PPs. Furthermore, hPPAR alpha-6/29 could act as a dominant negative regulator of PPAR-mediated gene transcription. When introduced into primary rat liver cell cultures by transient transfection, hPPAR alpha-6/29 prevented the suppression of hepatocyte apoptosis by the PP nafenopin, but not that seen in response to phenobarbitone (PB), a non-genotoxic carcinogen whose action does not involve PPAR alpha. The suppression of hepatocyte apoptosis was abrogated completely even though only 30% of hepatocytes were transfected, suggesting the involvement of a soluble factor. Recent data have suggested that TNF alpha, perhaps released by liver Kupffer cells in response to PPs, may play a key role in mediating the effects of PPs on hepatocyte growth regulation.

Animals↗
PubMed1997

Stationary interphases with extended alkyl chains: a comparative study on chain order by solid-state NMR spectroscopy.

Stationary interphases with long n-alkyl chains (n = 18, 22, 30, 34) have been examined by solid-state NMR spectroscopy. The determination of the silane functionality and the degree of cross-linking of silane ligands on the silica surface was performed by 29Si CP/MAS NMR spectroscopy. High-speed 1H MAS and 13C CP/MAS NMR spectroscopy were utilized to assess alkyl chain order and mobility of the different bonded phases. For this purpose, 1H NMR line widths and 13C chemical shifts have been evaluated. It is shown that stationary phase order and rigidity increase with alkyl chain length. In addition, the temperature-dependent trans/gauche conformational change occurs at higher temperatures for a polymeric C34 phase compared with a C30 sorbent. This behaviour is discussed in the context of previously reported chromatographic (HPLC) shape selectivity differences.

Carbon Isotopes↗
PubMed1996

1H MAS NMR spectroscopy of chemically modified silica gels: a fast method to characterize stationary interphases for chromatography.

Chemically modified silica gels used as stationary phases in chromatography have been investigated by means of solid-state 1H magic angle spinning (MAS) NMR spectroscopy. Since the organosilanes are bonded to the surface of the silica gel, their protons are diluted and possess a higher mobility in comparison to protons in pure organic solids. Thereby the usually strong homonuclear dipole-dipole interactions among the protons are reduced and it is possible to obtain well-resolved 1H NMR spectra of the organic interphases with MAS-only techniques. Effects of temperature and magnetic field strength on the resolution of the spectra are examined as well as the dependence of T1 and T1pH relaxation times on temperature and spinning speed.

Chemical Phenomena↗
PubMed1995

Solid state NMR and extraction studies on "phenyl"-bonded stationary phases used for solid phase extraction.

The solid phase extraction (SPE) and elution of [14C]-propranolol from aqueous buffer has been studied for a range of phenyl-bonded SPE materials. Differences were noted in the recovery of the analyte using methanol-water eluents depending upon the manufacturer and whether or not phase had been endcapped. Efficient recoveries of [14C]-propranolol were only achieved when triethylamine was added to the eluting solvent as a competing base. Solid state cross polarisation/magic angle spinning (CP/MAS) NMR spectroscopy was used to characterise the phases further, which revealed differences in endcapping between materials as well as differences in the type and extent of cross-linking.

Magnetic Resonance Spectroscopy↗
PubMed1994

Recurrence of HIV-related tuberculosis in an endemic area may be due to relapse or reinfection.

SETTING: Two Research Clinics within Nairobi, Kenya, one in the Infectious Diseases Hospital, the national referral centre for tuberculosis, and one in a community based project in Pumwani district, and the Bacterial Molecular Genetics Unit at the London School of Hygiene and Tropical Medicine. OBJECTIVE: To determine whether recurrence of tuberculosis after 'adequate' treatment was due to reinfection with a different isolate of Mycobacterium tuberculosis or to relapse of the original infection. DESIGN: A retrospective comparison by DNA fingerprinting of sets of isolates of M. tuberculosis from patients with recurrence of tuberculosis and in whom isolates from the original episode had been stored was made. Five patients with recurrence of tuberculosis two to nineteen months after adequate treatment and documented clearance of disease were studied. RESULTS: In one patient, fingerprints of the isolates of M. tuberculosis from the recurrence were quite different to those from the original episode; in the other four, the fingerprints were identical. CONCLUSION: Reinfection rather than relapse was the cause of recurrence in at least one patient. The high 'relapse' rates seen in HIV-related tuberculosis in Africa may in part be due to increased susceptibility to reinfection and not to treatment failure.

AIDS-Related Opportunistic Infections↗
PubMed1994

Antimicrobial susceptibility and presence of extrachromosomal deoxyribonucleic acid in Salmonella and Shigella isolates from patients with AIDS.

The development of multi-drug resistance by enteric bacteria is an increasing problem in the developing countries. There is need to monitor antimicrobial susceptibility of these organisms in order to ensure appropriate treatment and control of infections. Antimicrobial susceptibility patterns, plasmid DNA content and restriction enzyme digests of plasmid deoxyribonucleic acid (DNA) were used to study 175 Salmonella and Shigella species isolated from predominantly HIV-seropositive adult patients in Nairobi, Kenya. All the isolates were sensitive to ciprofloxacin. A significantly higher proportion of Shigella species were resistant to chloramphenicol, cotrimoxazole, streptomycin and tetracycline compared to Salmonella species (p-value < 0.001). Multi-resistant Salmonella typhimurium isolates had 60, 40 and 5 MDa plasmids, the 5 MDa plasmid was absent in gentamicin sensitive isolates. In addition to 2-10 MDa range of plasmids, multi-resistant Shigella species had a heavy 100-105 MDa plasmid. Restriction enzyme digests were similar for the 60 and 40 MDa plasmid DNA bands from Salmonella typhimurium isolates but did not show any consistency among Shigella spp. Plasmid-encoded multi-drug resistance plays a major role in the spread of resistance among enteric bacteria. It is vital to use drugs rationally in order to control the emergence and spread of multi-drug resistance.

AIDS-Related Opportunistic Infections↗
PubMed1993

Increased recurrence of tuberculosis in HIV-1-infected patients in Kenya.

There is evidence that in human immunodeficiency virus 1 (HIV-1) infected patients with tuberculosis the rate of recurrence of tuberculosis is increased in those patients treated with a standard thiacetazone-containing regimen. To assess the impact of HIV-1 on tuberculosis in Kenya, patients with tuberculosis were studied prospectively. After treatment with either a standard thiacetazone plus isoniazid regimen or a short-course thiacetazone-containing regimen, overall recurrence rate of tuberculosis was 34 times greater in 58 HIV-1-positive patients than in 138 HIV-1-negative patients (adjusted rate ratio 33.8, 95% CI 4.3-264). Recurrence in the HIV-1-positive group was strongly associated with a cutaneous hypersensitivity reaction due to thiacetazone during initial treatment (rate ratio 13.2, 95% CI 3.1-56.2). In all patients with a cutaneous hypersensitivity reaction ethambutol was substituted for thiacetazone. No significant association was found between recurrence among HIV-1-positive patients and initial resistance, initial treatment regimen, a diagnosis of AIDS (WHO definition), or poor compliance. DNA fingerprinting suggested that both relapse and new infection may have produced recurrence of tuberculosis. In patients who had a cutaneous hypersensitivity reaction, increased recurrence rate may have been related to interruption of treatment, subsequent poor compliance, or more advanced immunosuppression. Alternatively, a change to the combination of ethambutol and isoniazid in the continuation phase for 11 months only may not be adequate.

AIDS-Related Opportunistic Infections↗
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

Local street speed management in Australia--is it "traffic calming"?

A small sample of recent developments in local speed management and safety in Australia is outlined to illustrate conclusions about practice and assessment. This experience seems to support the effectiveness of devices in lowering speeds and reducing accidents, but there is still generally a lack of adequate monitoring and evaluation. Speeds in new residential areas require attention in the planning and design stages; some current fads in neighbourhood planning threaten to perpetuate old traffic problems. The current use of the term traffic calming to mean reduction of car travel demand rather than restraint on driver behaviour and route choice is noted. It is suggested that citywide suppression of traffic goes beyond "traffic calming" as it is commonly understood, into the realm of travel demand management and cultural change.

Accidents, Traffic↗
PubMed1992

Cross-sectional survey of HIV infection among patients with tuberculosis in Nairobi, Kenya.

Evidence from many countries suggests an association of human immunodeficiency virus (HIV) infection and tuberculosis of major public health significance. In order to begin assessing the impact of HIV on tuberculosis in Kenya, we have determined the HIV-1 seroprevalence among tuberculosis patients and compared the clinical characteristics of tuberculosis in HIV-positive and HIV-negative patients in two cross-sectional studies at the Infectious Disease Hospital (IDH) and the Ngaira Avenue Chest Clinic (NACC), Nairobi, Kenya. The diagnosis in 92% of all patients with pulmonary tuberculosis was confirmed by culture. The remainder were diagnosed on histological, clinical or radiological grounds. HIV seroprevalence among tuberculosis patients at IDH was 26.5% (52/196) compared to 9.2% (18/195) at NACC (P less than 0.001). There was no association between numbers of streptomycin injections in the previous 5 years and HIV infection. Positive sputum smear rates in HIV-positive patients were slightly lower than in HIV-negative patients at both study sites (71% vs 83% at IDH and 73% vs 82% at NACC) but the difference was not significant. Only Mycobacterium tuberculosis was isolated. Miliary disease was not associated with HIV infection. Persistent diarrhoea, oral candidiasis, generalized itchy rash, herpes zoster and generalized lymphadenopathy were all associated with HIV infection, but 46% (95% CI:38-54%) of all HIV-positive patients had none of the clinical features listed in the WHO Clinical Criteria for the Diagnosis of AIDS, apart from fever, cough and weight loss. Stevens-Johnson Syndrome was reported in 7/52 (13%) patients with HIV infection, and in 4/144 (3%) patients without (RR 4.85, 95% CI: 1.45-15.88).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Cohort study of HIV-positive and HIV-negative tuberculosis, Nairobi, Kenya: comparison of bacteriological results.

We have set up a cohort of human immunodeficiency virus (HIV) positive and negative patients with tuberculosis in order to address the problems associated with HIV-related tuberculosis. We present here the results of sputum smear microscopy, culture, mycobacterial identification tests and drug susceptibility assays from specimens taken at presentation. In this selected population of largely pulmonary tuberculosis cases, HIV infection is not associated with significant differences in sputum smear positivity rate, culture positivity rate or initial drug resistance. No atypical mycobacteria were found. Direct sputum smear examination remains specific for the diagnosis of tuberculosis in Kenya in spite of the presence of HIV. HIV infection was not associated with an increase in the proportion of pulmonary cases still culture-positive at 6 months. However a significant increase in the proportion of cases still culture-positive at 6 months was seen in those with initially resistant strains and also in those treated with standard regimen (streptomycin, thiacetazone and isoniazid for 1 month followed by thiacetazone and isoniazid for 11 months, 1STH/11TH) rather than a short-course, rifampicin-containing regimen (rifampicin, pyrazinamide and isoniazid for 2 months, together with streptomycin for the first month and followed by 6 months of thiacetazone and isoniazid, SHRZ/6TH).

Cohort Studies↗
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↗