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Biomedical subjects

N I Paton

Publications and source records attributed to N I Paton.

29 records · Page 2Linked to original sources

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↗

Impact of tuberculosis on the body composition of HIV-infected men in Brazil.

OBJECTIVE: Tuberculosis (TB) is the commonest HIV-related opportunistic infection in many developing countries and is thought to be a frequent underlying cause of HIV-associated wasting. We have used reference water dilution methods to examine the body composition changes associated with TB and to assess the severity and pattern of wasting. METHODS: The study was conducted at a charitable support house for poor and homeless HIV-infected people in Rio de Janeiro, Brazil. Male patients who were HIV-positive and receiving treatment for active TB (HIVTB+) and HIV-infected controls without TB (HIVTB-) were studied. Total body water (TBW) and extracellular water (ECW) were measured by giving oral doses of deuterium oxide and sodium bromide, respectively, and determining enrichment in plasma after 4 hours. Intracellular water (ICW), body cell mass (BCM), lean body mass (LBM) and fat mass were calculated from these parameters using standard equations. RESULTS: HIVTB+ (n = 11) and HIVTB- (n = 12) groups were similar in age, height, CD4 count and HIV risk factors. HIVTB+ men had significantly lower mean ICW (13.2 versus 16.6 kg; p = .02) and BCM (18.4 versus 23.0 kg; p = .02), a relative expansion of ECW (35.0 versus 30.0 L/kg body weight; p = .04), and small and nonsignificant reductions in total body weight (58.0 versus 62.1 kg; p = .26), LBM (45.5 versus 47.7 kg; p = .33) and fat mass (12.5 versus 14.4 kg; p = .51) compared with HIVTB- controls. BCM in the HIVTB+ group was similar to reference values for severe malnutrition. The relative depletion of BCM appeared excessive in comparison with reference values for uncomplicated starvation. CONCLUSION: The nutritional status of HIVTB+ patients was significantly worse than HIVTB- patients. Body weight and LBM underestimated the nutritional deficit, and measurement of BCM is therefore necessary to appreciate the extent of malnutrition in such patients. Malnutrition in HIVTB+ patients is severe and may therefore contribute to decreased survival. Hypermetabolism appears to play a role in the wasting process in patients coinfected with HIV and TB.

AIDS-Related Opportunistic Infections↗

Multiple frequency bioelectrical impedance analysis: a cross-validation study of the inductor circuit and Cole models.

It has been proposed that multiple frequency bioelectrical impedance models of the human body should include an inductive property for the circulatory system, the inductor circuit model (ICM), and that such a model, when coupled with a new method of data analysis, can improve the predictive power of multiple frequency bioelectrical impedance analysis (MFBIA). This hypothesis was tested using MFBIA measurements and gold standard measures of total body and extracellular water volumes in a cross-validation study in two subject groups (viz. controls and HIV). The MFBIA measurements were analysed using the current, widely accepted Cole model and the alternative ICM model which includes an inductive component. Correlations in the range 0.75 to 0.92 (for TBW) and 0.46 to 0.79 (for ECW) for impedance quotients versus gold standard measures within the subject groups were observed. These decreased, to as low as r = 0.50 for TBW and r = 0.29 for ECW, when the derived algorithms were applied to the alternative subject group. These results suggest that lack of portability of MFBIA algorithms between subject groups is not due to an inadequacy of the analogue circuit model per se but is possibly due more to fundamental flaws in the principles associated with its application. These include assuming a constant proportionality of body segment geometries and tissue fluid resistivities. This study has also demonstrated that this inadequacy cannot be overcome by simply introducing an inductive component into the analogue electrical circuit.

Algorithms↗

Bioelectrical impedance analysis in human immunodeficiency virus-infected patients: comparison of single frequency with multifrequency, spectroscopy, and other novel approaches.

Bioelectrical impedance (BIA), a prediction method for estimating body water compartments and body cell mass (BCM), is being increasingly used in studies of human immunodeficiency virus (HIV)-related wasting, but there are few validation studies of the method in this group. The aim of this study is to examine the relationship between impedance measurements and body water compartments in patients with advanced HIV disease, and to investigate whether the newer approaches of multifrequency BIA, BIA spectroscopy, logarithmic transformation using a parallel circuit model, and direct calculation from electrical theory offer any advantage over traditional single-frequency BIA. We measured total body water (TBW) by deuterium dilution and extracellular water by bromide dilution in 33 patients with advanced HIV disease. Intracellular water and BCM were calculated from these results. Impedance was measured over a range of frequencies using a multifrequency analyzer. The relationship between impedance index at various frequencies and body water compartments was assessed by correlation and linear regression. We found that impedance index at higher frequencies had a closer relationship to TBW (r = 0.86, standard error of the estimate [SEE] = 2.96 at 1000 kHz) and at lower frequencies a closer relationship to extracellular water (ECW) (r = 0.47, SEE = 3.13 at 0 kHz) than the traditional 50 kHz measurement (r = 0.84, SE = 3.11 for TBW; r = 0.44 SEE = 3.19 for ECW), but the differences were marginal and not statistically significant. None of the other novel approaches tested were significantly better than traditional single frequency measurement. The 50 kHz equation for BCM developed in this study [BCM (kg) = (0.360331 x Ht2/Z50) + (0.151123 x Wt)-2.95] may be useful to investigators using BIA for hIV-wasting studies.

Acquired Immunodeficiency Syndrome↗

Longitudinal changes in body composition measured with a variety of methods in patients with AIDS.

We test the hypothesis that human immunodeficiency virus (HIV)-related weight loss is accompanied by inappropriately large losses of fat-free mass (FFM). Our secondary aims were to examine whether FFM increases during weight gain and to compare several techniques for measuring FFM change. FFM was measured at intervals averaging 5 months in 21 AIDS patients by means of skinfold thickness (SF), dual-energy x-ray absorptiometry (DEXA), total body water (TBW), and bioelectrical impedance using the equation of the manufacturer of the equipment (BIA(EZComp)) and a published prediction equation (BIA(Segal)). The FFM content of weight loss was similar for SF (57%), DEXA (60%), TBW (55%) and BIA(EZComp) (65%), but the result from BIA(Segal) (78%) was higher. The results were close to predicted starvation values apart from the results with BIA(Segal), which were significantly higher than predicted values. Weight gain was also composed of a large proportion of FFM. There were large intermethod differences in measurements of absolute FFM, but for measuring changes in FFM, the bias between SF, DEXA, and TBW was minimal. The results of BIA vary with the prediction equation used. In this group of patients with the acquired immune deficiency syndrome (AIDS), weight loss was composed of a large proportion of FFM, but in general this is compatible with undernutrition as the underlying cause and does not support the hypothesis of excessive FFM catabolism in HIV disease. SF, DEXA, TBW, and BIA(Segal) show reasonable agreement for measuring body composition changes. This information should be considered in the design of future intervention studies for HIV-related wasting.

Absorptiometry, Photon↗

Bone mineral density in patients with human immunodeficiency virus infection.

The Object of this study was to determine whether HIV infection is associated with decreased bone mineral density (BMD). BMD was measured by dual-energy X-ray absorptiometry at total body, lumbar spine, and hip in 45 men with HIV infection and compared with sex, age, and weight-matched controls. Repeat scans were performed after a mean interval of 15 months in 21 patients to determine whether there were detectable losses of BMD. Compared with controls, the HIV patients had marginally lower BMD at the lumbar spine (P = 0.04) but there was no significant difference in total body or hip BMD. None of the patients had reduced BMD to levels associated with a diagnosis of osteoporosis. On longitudinal follow-up, a small decrease in total body BMD (-1.6%; P = 0.02) was observed but there was no significant change in spine and hip BMD. In spite of the many features of HIV infection that might be expected to cause a reduction in BMD such as cytokine activation, decreased physical activity, small bowel disease, hypogonadism, and direct infection of osteogenic cells by HIV, we found only minimal differences in BMD between HIV patients and controls. Furthermore, the HIV patients studied did not appear to show excessive loss in bone mineral over time.

Absorptiometry, Photon↗

Infections in systemic lupus erythematosus patients.

Infection is a frequent problem in patients with systemic lupus erythematosus (SLE), especially in those hospitalised with complications of disease. Infections contribute greatly to the morbidity of patients and are one of the commonest causes of death. The high frequency and unusual spectrum of infections can be attributed to the multiple disturbances of immune function in SLE in combination with the effects of immunosuppressive therapy. High doses of corticosteroids are particularly implicated as a risk factor for infection, although cyclophosphamide may also play a role. The majority of infections where a pathogen can be identified are due to typical gram-positive and negative bacteria. However, there is increasing evidence to indicate that opportunistic infections make a large contribution to the infectious mortality in SLE. Opportunistic infections are considerably under-reported due to difficulties in diagnosis pre-mortem and the fact that they can mimic or be superimposed upon active lupus. The presenting features of tuberculosis, listeriosis, nocardiosis, candidiasis, cryptococcal meningitis, Pneumocystis carinii pneumonia and invasive aspergillosis in patients with SLE are discussed in this review, with particular attention to presentation in SLE patients in Asia. Heightened awareness of the potential for opportunistic pathogens to infect SLE patients, together with earlier investigation and appropriate therapy for such infections, are likely to make a significant contribution to decreasing the mortality in patients with SLE.

Asia↗

Total energy expenditure and physical activity measured with the bicarbonate-urea method in patients with human immunodeficiency virus infection.

1. Our objectives were to measure total energy expenditure, the daily variation in total energy expenditure and the physical activity level in a group of HIV-positive subjects using the bicarbonate-urea method. The study also aimed to asses the practicalities of using the bicarbonate-urea technique in free-living conditions. 2. Total energy expenditure was measured with the bicarbonate-urea method over 2 consecutive days (1 day in one subject) in 10 male patients with HIV infection (median CD4 count = 30). Resting energy expenditure was measured by indirect calorimetry. Physical activity level (total energy expenditure/resting energy expenditure) was calculated from these measurements and from activity diaries. 3. Resting energy expenditure was found to be 7.46 +/- 0.87 MJ/day, 5% higher than predicted values. Total energy expenditure was 10.69 +/- 1.95 MJ/day with an intra-individual day-to-day variation of 6 +/- 6%. The measured physical activity level was 1.42 +/- 0.14, higher than the diary estimate of 1.34 +/- 0.16 (P = 0.029), and there were large intermethod differences in individual values. The subcutaneous infusion of bicarbonate was well tolerated and did not seem to restrict normal activities. 4. Total energy expenditure was not elevated in the group of HIV-positive subjects when compared with reference values for normal subjects. The physical activity level of the patients in this study was lower than that measured using other techniques in healthy young men, but was compatible with that expected for people leading a sedentary lifestyle. Reductions in physical activity in patients with HIV are likely to contribute to the wasting process and physical activity level may thus be a clinically useful measure. This study has also provided the first tracer estimate of the day-to-day variation in total energy expenditure. The bicarbonate-urea method represents an important new investigative tool for measuring total energy expenditure which has previously only been possible within the confines of a whole-body calorimeter or using the expensive doubly labelled water method.

Adult↗

Risk factors for infection in Malaysian patients with systemic lupus erythematosus.

To determine the incidence, types and risk factors for infection in systemic lupus erythematosus (SLE) patients in Kuala Lumpur, Malaysia, we retrospectively reviewed the medical records of 102 patients with definite SLE attending a specialist clinic. Details of major infections (pneumonia or severe infection requiring intravenous therapy) and minor infections, and their time of onset in relation to immunosuppressive therapy and disease flares were recorded. There were 77 major and 163 minor infections during 564 patient-years of follow-up. In the month following a course of pulse methylprednisolone, the incidence of major infection was 20 times higher and the incidence of minor infection was 10 times higher than at other periods (p < 0.0001). In the month after disease flare, the incidence of major infection was 10 times higher and the incidence of minor infection six times higher than at other times (p < 0.0001). After allowing for methylprednisolone therapy and disease flares, there was no increase in the rate of infections during treatment with azathioprine, oral or intravenous cyclophosphamide. There was no effect of renal involvement on infection rate.

Adolescent↗

Mortality in Malaysians with systemic lupus erythematosus.

One hundred and two patients attending the systemic lupus erythematosus (SLE) clinic of the Department of Medicine, Universiti Kebangsaan Malaysia, were studied retrospectively to determine their survival rates and causes of death. There were 21 deaths. The 1, 5, and 10 year survival rates were 93%, 86% and 70% respectively. There was a bimodal pattern of mortality with more patients dying in the first 2 years or after 5 years of disease. Infection was the direct cause of death in 52% and contributed to a further 19% of deaths. Patients with lupus nephritis had a higher relative risk (RR) of death (RR = 4.34, p < 0.02) although there was no significant increase in risk with any particular histological type on biopsy. Cerebral lupus (RR = 3.08, p < 0.001) and methylprednisolone treatment (RR = 6.24, p < 0.001) were also associated with increased risk of death. Increased awareness of infection and earlier use of antibiotic therapy may improve survival of patients suffering from SLE.

Adolescent↗