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Biomedical subjects

N I Paton

Publications and source records attributed to N I Paton.

At least 19 recordsLinked to original sources
PubMed2005

Association of Mycobacterium tuberculosis Beijing genotype with tuberculosis relapse in Singapore.

The relationship of Mycobacterium tuberculosis Beijing genotype with tuberculosis relapse was examined. Beijing strains were detected from 32 out of 45 (71%) relapsed cases and 148 out of 290 (51%) non-relapsed cases. Multivariate logistic regression analysis revealed that Beijing genotype was significantly associated with tuberculosis relapse (OR 2.64, 95% CI 1.30-5.34, P=0.005).

Adolescent↗
PubMed2005

Hydroxychloroquine, hydroxyurea and didanosine as initial therapy for HIV-infected patients with low viral load: safety, efficacy and resistance profile after 144 weeks.

OBJECTIVES: To evaluate the long-term safety and efficacy of the combination of hydroxychloroquine, hydroxyurea and didanosine. METHODS: We recruited antiretroviral-naive patients with viral loads less than 100 000 HIV-1 RNA copies/mL and CD4 counts greater than 150 cells/microL. All patients received hydroxychloroquine (200 mg), hydroxyurea (500 mg) and didanosine (125-200 mg) twice daily. Clinical and laboratory safety assessments and measurements of viral load and CD4 count were made at regular intervals, and genotypic resistance testing was performed on samples with detectable viral load at 48, 96 and 144 weeks. RESULTS: Fourteen of the 17 patients who commenced therapy remained on treatment at 144 weeks. Treatment was well tolerated but caused neutropenia, usually mild and transient, in 12 patients (71%). Mean viral load was reduced by 1.6 log(10) copies/mL below baseline (P<0.001), eight patients (47%) had undetectable viral load (<400 copies/mL), and two patients (12%) had detectable viral load but no detectable resistance mutations at week 144. Four patients (24%) had detectable viral load together with major resistance mutations (three with both 74 V and 184 V, and one with both 62 V and 65R) at week 144, but still had viral load suppression below baseline. Mean CD4 count was increased by 106 cells/microL above baseline (P=0.07) at week 144. CONCLUSIONS: This novel and well-tolerated combination controls viral replication during long-term follow up, with development of few resistance mutations. With careful monitoring it may be a useful strategy for delaying highly active antiretroviral therapy (HAART) and associated toxicity in selected patients with low initial viral loads.

Adult↗
PubMed2005

Laser scanning as a tool for assessment of HIV-related facial lipoatrophy: evaluation of accuracy and reproducibility.

BACKGROUND: Facial lipoatrophy (LA) is a common complication of highly active antiretroviral therapy (HAART). Research into causes and treatment of facial LA is hindered by the lack of an objective measurement tool. OBJECTIVE: To evaluate the accuracy and reproducibility of three-dimensional laser scanning (LS) for estimating cheek volume changes. METHODS: Paired laser scans were performed and the images superimposed using commercial software. The volume difference between images was computed within a circle of radius 25 mm placed in a standardized position over the cheek area. Accuracy was tested by scanning before and after known volumes of plasticine (0.5--5 mL) were applied to the cheek area of a mannequin to simulate volume change. Reproducibility was tested by repeated scanning of the mannequin with and without 2 mL of plasticine, and repeated scanning of 10 healthy subjects over the course of 1 week. RESULTS: The mean difference between actual and estimated volume change was small across the range of volumes tested [mean difference 0.08 mL; 95% confidence interval (CI)-0.36 to 0.20 mL). The coefficient of variation for repeated measurements of 2-mL volume change was 5.8%. The intraclass correlation coefficient for scan-to-scan variability was 0.812 (95% CI 0.515--0.947) and for day-to-day variability it was 0.764 (95% CI 0.332--0.935). Conclusions LS is an accurate and reproducible method for estimating cheek volume changes. It may be useful as an objective tool for assessment of facial LA in clinical research studies.

Antiretroviral Therapy, Highly Active↗
PubMed2005

A randomised controlled trial of oral zinc on the immune response to tuberculosis in HIV-infected patients.

SETTING: The National HIV Unit, Singapore. OBJECTIVE: To test whether zinc supplementation improves the immune response to tuberculosis in HIV-positive patients. DESIGN: A double-blind, randomised, placebo-controlled trial of 28 days of oral zinc sulphate (50 mg of elemental zinc) or placebo in stable adult HIV-positive patients receiving antiretroviral therapy with a CD4 count <200 cells/microl. METHODS: IFN-gamma response to mycobacterial antigen stimulation, CD4/8 cell count, lymphocyte subsets, T-cell receptor excision circle (TREC) levels and viral load were measured at baseline and day 28. RESULTS: Thirty-two patients received zinc and 34 placebo. There was no significant change in the IFN-gamma response to human PPD stimulation in the zinc or placebo groups (placebo baseline: 0.42 +/- 1.03, day 28: 0.84 +/- 1.21 IU/ml, zinc baseline: 1.26 +/- 2.41, day 28: 1.39 +/- 1.88 IU/ml, P = 0.31 between groups), nor any of the other mycobacterial antigens tested. There were no changes in absolute CD4/8 cell levels or other lymphocyte subsets, TREC or viral load. Baseline zinc levels were normal in 62/66 (93.9%) patients. CONCLUSIONS: We found no evidence for recommending pharmacological supplementation with oral zinc in HIV-positive patients without zinc deficiency.

Administration, Oral↗
PubMed2004

Prevalence of and risk factors for nasal colonization with Staphylococcus aureus among human immunodeficiency virus-positive outpatients in Singapore.

We studied the prevalence of and risk factors for Staphylococcus aureus nasal colonization in HIV-positive outpatients in Singapore. Overall prevalence was 23% (45 of 195), with 3% (6 of 195) being MRSA. Recent antibiotic use and hospitalization were independent predictors of MRSA colonization. Isolates were genotypically identical to our hospital's inpatient circulating strain.

HIV Infections↗
PubMed2004

Causes of death among patients with HIV in Singapore from 1985 to 2001: results from the Singapore HIV Observational Cohort Study (SHOCS).

OBJECTIVES: To investigate the major primary and contributory causes of death among HIV patients in Singapore. DESIGN: A retrospective observational cohort study of all adult patients seen at the national referral centre for HIV in Singapore between 1985 and 2001. METHODS: Data were extracted from the patients' records by 10 trained health care workers. AIDS-defining conditions were established using predefined criteria. For each case, a single principal cause of death and up to three contributory causes were identified. RESULTS: A total of 1504 patients aged 17 years or over were seen before the end of 2001, of whom 504 have died. The most frequent principal causes of death were Mycobacterium avium (17.5%), Mycobacterium tuberculosis (9.7%), pneumonia (cause unknown) (6.5%) and Cryptococcus neoformans (6.7%). Three hundred and eighteen patients (63.1%) died from an AIDS-defining condition. CONCLUSIONS: The causes of death were similar to those found in Western cohorts, except that disseminated M. avium was a more frequent cause of death.

AIDS-Related Opportunistic Infections↗
PubMed2004

Importation of seven cases of an unusual helminthic infection into Singapore and assessment of the risk of local transmission.

Singapore remains vulnerable to the introduction of infectious diseases from other countries due to the high traffic of migrant labour and other visitors. We describe seven cases of migrant workers from West Africa who entered Singapore carrying loaisis, a helminthic infection. The clinical presentation, treatment using single dose ivermectin, potential for transmission, and the need for screening of this infection in Singapore are discussed.

Adult↗
PubMed2003

A pilot study of the safety and efficacy of thymosin alpha 1 in augmenting immune reconstitution in HIV-infected patients with low CD4 counts taking highly active antiretroviral therapy.

To study the safety and efficacy of thymosin alpha1 in stimulating immune reconstitution in combination with highly active antiretroviral therapy (HAART), a phase II randomized, controlled open-label trial of subcutaneous thymosin alpha1 was undertaken for 12 weeks. Twenty clinically stable patients with viral loads <400 copies/ml and CD4 counts less than 200 cells/microl were randomized to receive 3.2 mg thymosin alpha 1 subcutaneous injections twice weekly or no injections for 12 weeks. CD4 and CD8 counts, CD45 RO+ and RA+ subsets and signal joint T cell receptor excision circles (sjTREC) in peripheral blood mononuclear cells (PBMCs) were measured every 2 weeks. Thirteen patients received thymosin alpha 1 and seven were controls. Thymosin alpha 1 was well tolerated and there were no serious adverse events. There was no significant difference between the thymosin alpha1 and control groups in CD4, CD8 and CD45 lymphocyte subset changes at week 12; however, PBMC sjTREC levels increased significantly in the thymosin alpha 1-treated patients compared to controls at week 12. In conclusion, the increase in PBMC sjTREC levels in patients taking thymosin alpha1 may represent enhanced immune reconstitution; however, the clinical benefits and long-term consequences remain to be determined.

Adult↗
PubMed2003

Late clinical and magnetic resonance imaging follow up of Nipah virus infection.

The Nipah virus is a newly identified paramyxovirus responsible for an outbreak of fatal encephalitis in Malaysia and Singapore. This paper reports the follow up clinical and magnetic resonance imaging findings in 22 affected subjects. Of 13 patients with encephalitis, one died, one was lost to follow up, and seven recovered. Among the four remaining patients, one had residual sixth nerve palsy, another suffered from severe clinical depression, and a third patient had evidence of retinal artery occlusion. One patient with delayed onset Horner syndrome had a single lesion in the cervical spinal cord. The brain magnetic resonance findings were stable or improved in nine patients over 18 months of follow up. Among a second group of nine asymptomatic seropositive abattoir workers, magnetic resonance examination in seven subjects revealed discrete small lesions in the brain; similar to those detected in encephalitis patients. These findings suggest that in addition to encephalitis, the newly discovered Nipah virus affects the spinal cord and the retina. Late clinical and radiological findings can occur in Nipah virus infections as with other paramyxoviruses.

Abducens Nerve Diseases↗
PubMed2002

A survey of Nipah virus infection among various risk groups in Singapore.

Following the Nipah virus (NV) outbreak in March 1999 in Singapore, a serological survey was undertaken to screen individuals potentially exposed to NV. Blood samples were tested for NV IgM, IgG and neutralizing antibodies. Twenty-two (1.5%) of 1469 people tested had antibodies suggesting NV infection. Although 12 of the 22 infected people (54.6%) were symptomatic, the remaining 10 (45.4%) were clinically well and had no past history of compatible pulmonary or neurological disease. Clinical and serological findings suggested three people had been infected with NV before the outbreak was recognized. All those who were infected were male abattoir workers. None of the people who had contact with horses, and no healthcare workers exposed to infected patients and their specimens had detectable antibodies. This study provides evidence that NV causes asymptomatic infection. All of the antibody positive individuals had direct contact with pigs and there was no evidence of human to human transmission.

Abattoirs↗
PubMed2001

Protein and energy metabolism in chronic bacterial infection: studies in melioidosis.

Chronic infection is often accompanied by a wasting process, the metabolic basis of which is not fully understood. The aims of the present study were to measure protein and energy metabolism in patients with melioidosis (a serious and antibiotic-refractory Gram-negative bacterial infection which is endemic in South-East Asia) in order to define the metabolic abnormalities that might contribute to wasting. Whole-body protein turnover was measured using the [(13)C]leucine technique, both in the fasted state and while consuming a high-energy meal. Resting energy expenditure was measured by indirect calorimetry, and total energy expenditure by the bicarbonate/urea method. Results were normalized for fat-free mass, as estimated from skinfold thickness. Protein turnover was increased in melioidosis patients compared with healthy controls during fasting (170.9 compared with 124.1 micromol x kg(-1) x h(-1); P=0.04), but the net rate of catabolism (22.2 compared with 20.5 micromol x kg(-1) x h(-1); P=0.77) and the anabolic response to feeding were similar in the two groups. Resting energy expenditure was higher in melioidosis patients compared with controls (191.4 and 157.3 kJ x kg(-1) x day(-1) respectively; P=0.04), but total energy expenditure (measured in a separate group of eight patients with melioidosis) was low (192.1 kJ x kg(-1) x day(-1)). In conclusion, this study found no evidence of metabolic causative factors, such as accelerated net protein catabolism during fasting, a blunted anabolic response to feeding or increased daily energy expenditure, and therefore suggests that reduced energy intake is the prime cause of wasting. The observed normal response to feeding should encourage nutritional approaches to prevent wasting.

Adult↗
PubMed2000

Cryptococcal meningitis resulting in irreversible visual impairment in AIDS patients--a report of two cases.

Cryptococcus neoformans is the leading cause of meningitis in patients with Acquired Immune Deficiency Syndrome (AIDS) and is associated with high mortality rate. Presenting symptoms include fever, nausea and vomiting, altered mentation, headache and meningismus. Cryptococcal meningitis is not infrequently complicated by raised intracranial pressure and visual sequelae (sometimes by blindness). In patients who survive the infection, the most debilitating outcome appears to be visual impairment or blindness. Management of impending visual complication combines medical and surgical treatment modalities. We report two cases of cryptococcal meningitis associated with visual impairment.

AIDS-Related Opportunistic Infections↗
PubMed1999

Outbreak of Nipah-virus infection among abattoir workers in Singapore.

BACKGROUND: In March 1999, an outbreak of encephalitis and pneumonia occurred in workers at an abattoir in Singapore. We describe the clinical presentation and the results of investigations in these patients. METHODS: Clinical and laboratory data were collected by systemic review of the case records. Serum and cerebrospinal fluid (CSF) samples were tested for IgM antibodies to Nipah virus with an IgM capture ELISA. Reverse-transcriptase PCR was done on the CSF and tissue samples from one patient who died. FINDINGS: Eleven patients were confirmed to have acute Nipah-virus infection based on raised IgM in serum. Nipah virus was identified by reverse transcriptase PCR in the CSF and tissue of the patient who died. The patients were all men, with a median age of 44 years. The commonest presenting symptoms were fever, headache, and drowsiness. Eight patients presented with signs of encephalitis (decreased level of consciousness or focal neurological signs). Three patients presented with atypical pneumonia, but one later developed hallucinations and had evidence of encephalitis on CSF examination. Abnormal laboratory findings included a low lymphocyte count (nine patients), low platelet count, low serum sodium, and high aspartate aminostransferase concentration (each observed in five patients). The CSF protein was high in eight patients and white-blood-cell count was high in seven. Chest radiography showed mild interstitial shadowing in eight patients. Magnetic resonance imaging (MRI) showed focal areas of increased signal intensity in the cortical white marker in all eight patients who were scanned. The nine patients with encephalitis received empirical treatment with intravenous aciclovir and eight survived. INTERPRETATION: Infection with Nipah virus caused an encephalitis illness with characteristic focal areas of increased intensity seen on MRI. Lung involvement was also common, and the disease may present as an atypical pneumonia.

Abattoirs↗
PubMed1999

Short-term growth hormone administration at the time of opportunistic infections in HIV-positive patients.

OBJECTIVES: A 12-week course of recombinant human growth hormone is an effective but expensive therapy for established HIV-related wasting. Wasting in HIV disease is often episodic, coinciding with bouts of acute opportunistic infection. We hypothesized that a short course of growth hormone, targeted at the time of opportunistic infection, might improve protein metabolism thereby reducing lean tissue loss. METHODS: HIV-infected men with acute opportunistic infections, who received standard antimicrobial treatment for their infection as well as intensive nutritional counselling and oral energy supplements, were randomized to receive growth hormone or placebo for 14 days. Principal assessments were protein metabolism (measured by 13C-leucine infusion), body composition (measured by DEXA) and safety. RESULTS: There were no significant changes in outcome parameters in the placebo group (n = 11). In the growth hormone group (n = 9), protein catabolic rate decreased by 60% in the fasted state (P = 0.02 versus placebo), lean body mass increased by 2.2 kg (P = 0.03 versus baseline) and fat mass decreased by 0.7 kg (P = 0.002 versus baseline). There was no increase in adverse or serious adverse events in the growth hormone as compared with the placebo group. CONCLUSIONS: A two-week course of growth hormone at the time of acute opportunistic infection in HIV-infected patients improves protein metabolism and body composition during therapy and appears to be safe. This may represent a rational and economical approach to the use of growth hormone therapy.

AIDS-Related Opportunistic Infections↗