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Biomedical subjects

D C Macallan

Publications and source records attributed to D C Macallan.

At least 37 records · Page 2Linked to original sources
PubMed1997

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↗
PubMed1997

Measurement of NO synthesis in humans by L-[15N2]arginine: application to the response to vaccination.

Induction of nitric oxide (NO) synthesis is a key element of the inflammatory response in humans. We describe a sensitive gas isotope ratio mass spectrometric (GIRMS) method for measuring urinary [15N]nitrate production during intravenous infusion of L-[guanidino-15N2]arginine and its application to investigate the effects of a controlled inflammatory stimulus, typhoid vaccination, on NO synthesis in humans. Intravenous infusion of L-[15N2]arginine at 5-12 mumol.kg-1.h-1 for 24 h in three subjects was used to determine arginine and nitrate pool kinetics. Eight subjects received primed constant infusion of 2.5 mumol.kg-1.h-1 of L-[15N2]arginine for 12 h once before and again after typhoid vaccination. NO synthesis was calculated from 15N enrichment of plasma arginine and urinary nitrate, measured by gas chromatography mass spectrometry and GIRMS, respectively, and total urinary nitrate excretion. Baseline NO synthesis was 298 +/- 44 nmol.h-1.kg lean body mass-1, representing 0.41% of arginine flux. After vaccination, NO synthesis (267 +/- 77 nmol.h-1.kg-1) was not increased (P = 0.18), despite demonstration of an acute phase response. Typhoid vaccination is not accompanied by accelerated NO synthesis.

Adult↗
PubMed1996

The effect of endotoxin on skeletal muscle protein gene expression in the rat.

Sepsis is associated with net breakdown of skeletal muscle protein, mediated partly by reduced rates of muscle protein synthesis. This study investigated the role of altered gene expression for specific muscle proteins in mediating reduced protein synthesis in a rat model of acute severe sepsis. Adult rats were given a single sublethal intraperitoneal dose of endotoxin (bacterial lipopolysaccharide). Protein, RNA and DNA contents of muscle were measured and changes in expression of mRNA in tibialis anterior and extensor digitorum longus muscles were detected by quantification of Northern blots at 6, 24, 48 and 72 hr after endotoxin and in animals starved for 24 hr. Results showed that at 24 hr after endotoxin there was a loss of about 14% of muscle protein content. No reduction in mRNA was found at any time point for beta-myosin heavy chain (MHC), fast-MHC, alpha-actin, skeletal muscle troponin or carbonic anhydrase III (CA III); rather, at 48 hr there was increased expression of beta-MHC (224 +/- 123% control) and CA III (202 +/- 56%). Blocking TNF-alpha by pre-treatment with a monoclonal antibody did not appear to influence this. Total RNA content of muscle was reduced to 67% of the control values 24 hr after LPS, although this was no different to pair-fed animals starved for 24 hr. It is concluded that reduced protein synthesis in skeletal muscle in early acute sepsis is not primarily associated with reduced muscle protein gene expression.

Actins↗
PubMed1996

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↗
PubMed1996

Cutaneous and pharyngeal diphtheria imported from the Indian subcontinent.

We report the case of a 32-year-old woman who presented upon returning from India with cutaneous ulcers on the feet and pharyngitis. Microbiological testing showed the causative organism to be a toxigenic strain of Corynebacterium diphtheriae. She was treated successfully with penicillin and diphtheria antitoxin. This case emphasises the importance of maintaining a high index of suspicion for such rare but significant infectious diseases.

Adult↗
PubMed1995

Energy expenditure and wasting in human immunodeficiency virus infection.

BACKGROUND: Increased expenditure of energy at rest has been considered a contributing factor to the negative energy balance and weight loss that occur in patients with human immunodeficiency virus (HIV) infection. However, the true determinant of energy balance is not resting but total energy expenditure. We sought to determine the contribution of total energy expenditure to weight changes in patients with HIV-associated wasting. METHODS: We performed 51 assessments of energy metabolism in 27 men with HIV infection at different stages of disease, including periods of both rapid and slow weight loss. Resting energy expenditure was measured by indirect calorimetry, total energy expenditure by the doubly-labeled-water technique, and energy intake by recording the weight of food consumed. The results were compared with the rate of weight loss or gain. RESULTS: The mean (+/- SD) total energy expended by the HIV-infected men was 2750 +/- 670 kcal per day, no more than that expended by normal men. There was a significant positive relation between total energy expenditure and the rate of weight change (r = 0.61, P < 0.001); thus, during rapid weight loss, total energy expenditure was reduced to 2180 +/- 580 kcal per day (P = 0.009), primarily because of reduced physical activity. During rapid weight loss, the negative energy balance (-850 +/- 580 kcal per day) was primarily the result of the reduction in energy intake, to 1330 +/- 610 kcal per day; intake correlated strongly with the rate of weight change (r = 0.84, P < 0.001). CONCLUSIONS: In patients with HIV infection, total energy expenditure is reduced during episodes of weight loss. Reduced energy intake, not elevated energy expenditure, is the prime determinant of weight loss in HIV-associated wasting.

Adult↗
PubMed1995

Whole-body protein turnover from leucine kinetics and the response to nutrition in human immunodeficiency virus infection.

Whole-body protein metabolism was investigated in human immunodeficiency virus (HIV) infection by primed constant infusion of L-[1-13C]leucine in 8 control and 22 HIV-infected subjects (8 stage II; 14 stage IV disease), in postabsorptive and fed states. Postabsorptive leucine flux was increased 25% in subjects with stage IV HiV infection vs that in control subjects (130 +/- 13 vs 103 +/- 10 mumol leucine.kg-1.h-1, P < 0.001); both leucine disposal by protein synthesis (111.6 +/- 12.1 vs 82.3 +/- 9.2, P < 0.001) and release by protein degradation (129.7 +/- 13.1 vs 103.4 +/- 10.2, P < 0.001) were increased. No difference in leucine balance or oxidation was found but fat oxidation was greater in subjects with HIV infection (61.1 +/- 13.0% of energy) than in control subjects (47.6 +/- 13.7% of energy, P < 0.025). Stage II subjects had intermediate values of leucine flux, not significantly different from those of control subjects. Provision of parenteral nutrition for 4 h increased leucine flux with a switch in leucine balance from net loss to net gain; this response was quantitatively similar in all groups. HIV infection increases whole-body protein turnover but does not quantitatively impair the acute anabolic response to intravenous nutrition.

Adult↗
PubMed1994

Cardiac muscle protein gene expression in the endotoxin-treated rat.

1. Sepsis is associated with marked changes in cardiac muscle protein synthesis. Such changes may be the result of altered transcription of specific myofibrillar protein mRNAs. 2. In order to investigate myofibrillar protein gene expression, a rat model of sepsis was used. Adult rats were given a single sub-lethal dose of lipopolysaccharide by the intraperitoneal route. At various times thereafter, rats were killed and ventricular muscle was removed. RNA was extracted and transferred to nylon membranes. Changes in expression of mRNA for alpha- and beta-myosin heavy chain, alpha-actin, cardiac troponin C and carbonic anhydrase III were detected by Northern hybridization. 3. After treatment with lipopolysaccharide, mRNA for beta-myosin heavy chain increased to 260% of control values at 24 h and reached a maximum of 310% at 48 h. alpha-Myosin heavy chain mRNA levels fell to 72% of control values at 24 h. mRNA levels for alpha-actin, cardiac troponin C and carbonic anhydrase III remained unchanged. 4. In order to investigate the role of tumour necrosis factor-alpha in this process, some rats were pretreated with monoclonal antibody against tumour necrosis factor-alpha before receiving lipopolysaccharide. Such animals showed an absence of tumour necrosis factor-alpha bioactivity in plasma, but changes in myocardial protein mRNA levels were no different from those seen in animals receiving lipopolysaccharide alone. 5. The reduction in protein synthesis in cardiac muscle in sepsis does not appear to be the result of reduced expression of genes for structural or soluble muscle protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1993

Prospective analysis of patterns of weight change in stage IV human immunodeficiency virus infection.

Weight loss is a major manifestation of infection with the human immunodeficiency virus (HIV). Prospective analysis of weight change was performed in 30 male subjects with stage IV HIV infection over a period of 9-49 mo and weight change events (> 4 kg) related to contemporaneous clinical events. Two distinct patterns of weight loss were observed: episodes of acute severe weight loss and episodes of chronic unremitting progressive weight loss. Thirty-three acute episodes (median 9.1 kg in 1.7 mo) and 23 chronic episodes (13.2 kg in 9.5 mo) were identified. Twenty-seven of 33 (82%) acute weight-loss episodes were associated with nongastrointestinal opportunistic infections and 15 of 23 (65%) chronic episodes with gastrointestinal disease (P < 0.01). Weight loss was neither inevitable nor unremitting. Periods of weight stability (> 4 mo) occurred in 13 individuals (43%); 35 episodes of weight gain were identified, mostly related to recovery from opportunistic infection. These findings have important implications for our understanding of the natural history of weight loss in HIV infection.

Adult↗
PubMed1992

Osteomalacia should be sought and treated before withdrawal of anticonvulsant therapy in UK Asians.

Individuals from the Asian sub-continent in the United Kingdom are at particular risk of developing osteomalacia. We report a Gujarati woman who developed osteomalacia whilst taking anticonvulsant drugs; withdrawal of anticonvulsant therapy was followed by a seizure complicated by femoral neck fracture. In patients with other risk factors for osteomalacia, as is the case for Asians living in Britain, anticonvulsant drugs should not be reduced or withdrawn until osteomalacia, which puts the skeleton at increased risk of fracture, and its associated hypocalcaemia, which reduces seizure threshold, have been sought and adequately treated.

Adult↗
PubMed1992

Kinetics of endotoxin-induced acute-phase protein gene expression and its modulation by TNF-alpha monoclonal antibody.

The kinetics of cytokine release and acute-phase protein gene expression in liver were investigated in rats receiving a single intraperitoneal bolus dose of Escherichia coli lipopolysaccharide (LPS). Transient elevation of plasma tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were detected. Hepatic messenger RNAs for two acute-phase proteins, alpha 1-acid glycoprotein and alpha 2-macroglobulin, were measured by Northern blotting and were found to increase to a maximum at 24 h, returning to normal by 72 h; plasma concentrations showed a slower but more sustained rise. For albumin, hepatic mRNA was reduced, being minimum at 24 h with a similar but more prolonged fall in plasma concentration. Pretreatment of rats with TNF-alpha monoclonal antibody 4 h before LPS ameliorated weight loss and anorexia, partially suppressed the rise in IL-6 and reduced the increase in hepatic mRNA and plasma concentrations of alpha 1-acid glycoprotein and alpha 2-macroglobulin. For albumin, however, such pretreatment had no effect on the fall in either hepatic mRNA or plasma concentration. Thus we have defined an in vivo role of TNF-alpha in the control of endotoxin-induced acute-phase protein generation.

Acute-Phase Proteins↗
PubMed1990

Polyarteritis nodosa presenting as bilateral sudden onset cochleo-vestibular failure in a young woman.

Sudden onset sensorineural hearing loss is an otological emergency. Although deafness is recognised as being associated with polyarteritis nodosa (PAN) only very rarely does it herald the disease. We describe a case of bilateral, sudden onset vestibulo-cochlear failure which with thorough investigation proved to be the presenting complaint of PAN. This diagnosis enabled definitive management of a multi-system disorder and resulted in an improvement of the initial symptom with the chemotherapeutic regime discussed. We review the involvement of PAN in deafness and hope this case will remind otolaryngologists of the need for full investigation of the above mentioned emergency, in an attempt to discover and hence direct management towards a specific underlying pathology.

Adult↗
PubMed1990

The electrocardiogram in general practice: its use and its interpretation.

General practitioners in one health district were surveyed by postal questionnaire (including 15 sample electrocardiogram tracings) to assess their usage and competence in interpretation of the electrocardiogram. A response rate of 60% was achieved, of whom 40% said they used the electrocardiogram at least monthly and 43% used it 'always' or 'usually' in patients with suspected myocardial infarction at home. Overall competence in recognizing a variety of abnormalities was felt to be good. Recent qualification, the possession of a higher qualification (MRCP/MRCGP) and frequency of usage were associated with better performance. Even so, unequivocal acute myocardial infarction was misdiagnosed by 20% of respondents. These findings have implications for the provision of electrocardiographic services in primary care and the management of patients in the home with suspected myocardial infarction, particularly with the advent of thrombolytic therapy.

Clinical Competence↗
PubMedDate not supplied

Red cell exchange, erythrocytapheresis, in the treatment of malaria with high parasitaemia in returning travellers.

In severe falciparum malaria with high parasitaemia, removal of parasitized erythrocytes is generally considered to be of value as adjunctive therapy in addition to standard chemotherapy. Such removal is commonly achieved by exchange transfusion but this procedure is time-consuming and may be associated with haemodynamic disturbance. Current-generation automated cell-separator hardware and software allows prompt red cell exchange, erythrocytapheresis, in a single continuous-flow isovolaemic procedure. We describe the application of this procedure to 5 cases of severe falciparum malaria in travellers returning to the UK from the tropics. All patients also received quinine and conventional supportive therapy. In all cases, dramatic reduction in parasitaemia was achieved within 2 h with subsequent complete clinical recovery. Erythrocytapheresis has significant advantages over exchange transfusion in terms of speed, efficiency, haemodynamic stability and retention of plasma components such as clotting factors and may thus represent an improvement in adjunctive therapy for severe malaria.

Adolescent↗