Visual epilepsy in glioblastoma multiforme.

We report a 33-year-old Chinese gentleman who presented with visual epilepsy and symptoms of raised intracranial pressure in which clinical examination revealed normal visual fields and acuity despite Magnetic Resonance Imaging (MRI) brain showing large contrast enhancing mass at the right occipital lobe. Craniotomy and excision of tumour was done and the histology confirmed glioblastoma multiforme (GBM). He completed radiotherapy and recovered well except developing left inferior homonymous quadrantropia post operatively which improved with time.

Von Hippel angioma.

We report a three year follow up of a 35-year-old Indian gentleman who presented with sudden, painless blurring of left (L) eye vision with initial visual acuity (VA) of 6/60. Fundoscopy revealed (L) vitreous haemorrhage and subsequently confirmed a (L) inferotemporal capillary haemangioma. The adjacent area of capillary haemangioma was treated with barricade argon laser photocoagulation to prevent progression of exudative retinal detachment inferiorly. Subsequent follow up showed mild regression of capillary haemangioma with maintenance of (L) eye vision at 6/9.

A challenging case of malignant hypercalcaemia.

The investigation and management of patients presenting with hypercalcaemia is not always straightforward. We describe the case of a middleaged man presenting with severe symptomatic hypercalcaemia. The difficulties encountered here - in striving for biochemical and symptom control, and in establishing a definite diagnosis - are fortunately rare. The case illustrates the range of options in the treatment of severe hypercalcaemia, and highlights the use of haemodialysis in treatmentresistant cases.

Definition of endotoxin binding sites in horseshoe crab factor C recombinant sushi proteins and neutralization of endotoxin by sushi peptides.

Three truncated fragments, harboring different sushi domains, namely, sushi123, sushi1, and sushi3 domains, of Factor C were produced as biologically active secreted recombinant proteins. Sushi1 and 3 each has a high-affinity LPS binding site with K:(d) of 10(-9) to 10(-10) M. Positive cooperativity in sushi123 resulted in a 1000-fold increase in K:(d)2. The core LPS binding region of sushi1 and 3 reside in two 34-mer peptides, S1 and S3. A rigidly held disulfide-bonded structure is not essential but is important for LPS binding, as confirmed by a 100- to 10000-fold decrease in affinity. Both S1 and S3 can inhibit LAL reaction and LPS-induced hTNF-alpha secretion with different potency. LAL assay revealed that at least two molecules of S1 bind cooperatively to one LPS molecule, with Hill's coefficient of 2.42. The LPS binding by S3 is independent and noncooperative. The modified SDelta1 and SDelta3 peptides exhibited increased LPS neutralization potential although its LPS binding affinities indicated only a 10-fold improvement. Hence, the structural difference of the four sushi peptides conferred different efficiencies in LPS neutralization without altering their binding affinity for LPS. Circular dichroism spectrometry revealed that the four peptides underwent conformational change in the presence of lipid A, transitioning from a random coil to either an alpha-helical or beta-sheet structure. Two factors are critical for the sensitivity of Factor C to LPS: 1) the presence of multiple binding sites for LPS on a single Factor C molecule; and 2) high positive cooperativity in LPS binding. The results showed that in the design of an improved LPS binding and neutralizing peptide, charge balance of the peptide is a critical parameter in addition to its structure.

Energy expenditure in type 2 diabetic patients on metformin and sulphonylurea therapy.

Insulin and sulphonylurea therapies have both been reported to cause weight gain in Type 2 diabetic patients whereas metformin does not have this adverse effect. The mechanism for this difference is unclear. We have investigated in a cross-over study the effect of sulphonylurea and metformin therapy on energy expenditure and body composition in 10 Type 2 diabetic patients (7 females, 3 males) of various weights (mean body mass index 33.4 (SD 7.6 kg m-2)). Free living total energy expenditure was measured over 14 days by the doubly labelled water method adjusted for urinary glucose energy losses and resting energy expenditure by ventilated hood indirect calorimetry. Overall, total energy expenditure (12.88 +/- 4.17 vs 13.1 +/- 3.69 MJ 24 h-1) and resting metabolic rate (7.30 +/- 1.75 vs 7.23 +/- 1.74 MJ 24 h-1) were similar on metformin and sulphonylurea therapy, respectively. When adjusted for differences in fat free mass, resting metabolic rate on sulphonylurea therapy was slightly but significantly lower (mean difference -5.5 kJ 24 h-1 kg-1, 95% CI -1.2, -9.9 kJ 24 h-1 kg-1, p < 0.05). Fat free mass also increased significantly by 1.3 kg (95% CI 0.4, 2.4 kg, p < 0.05) when on sulphonylurea therapy, thus compensating for the lower resting metabolic rate per kg fat free mass to leave overall resting metabolic rate unchanged compared to metformin therapy. We also investigated the effect of adding metformin to six Type 2 diabetic patients already on insulin. This did not lead to any measurable changes in any of the components of energy expenditure.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of pharmacological dosages of glucocorticoids on free living total energy expenditure in man.

OBJECTIVES: Weight gain had previously been thought to be due to increased calorie intake alone though no information on its effect on total energy expenditure is available in humans. We therefore assessed whether weight gain associated with glucocorticoids is due to a reduction in energy expenditure. DESIGN: We performed an open study with 1 mg of betamethasone given orally twice a day for 21 days. SUBJECTS: Seven healthy female volunteers, age range 26-55 years, body mass index 19 to 40, mean 27 kg/m2. MEASUREMENTS: Total free living energy expenditure was measured by the doubly labelled water method (D2 18O), resting metabolic rate by ventilated hood indirect calorimetry and fat free mass from the dilution volume of oxygen-18 labelled water. Body composition and components of energy expenditure were assessed before and during the final 14 days of betamethasone administration. RESULTS: Weight increased by a mean of 1.2 kg (P < 0.05) because of a significant rise in fat mass (1.5 kg) with no change in fat free mass. Resting metabolic rate remained unaltered on betamethasone but total energy expenditure increased in all subjects with a significant mean rise of 26% from 11.7 to 14.7 MJ/24 h (P < 0.05). The energy component of physical activity with thermogenesis increased on average 52% (from 5.8 to 8.9 MJ/24 h; P < 0.05). The rise in energy expenditure was still apparent after correction for the increase in body weight. Fasting respiratory quotient (RQ) increased from 0.81 to 0.86 with no change in fasting blood glucose. Betamethasone did not result in an energy sparing effect on the two components of energy expenditure studied. CONCLUSIONS: Body weight increased on betamethasone entirely due to an increase in fat mass. This occurred despite a rise in total energy expenditure which involved specifically that component accounted for by physical activity plus thermogenesis. The most likely explanation is that betamethasone increased dietary energy intake significantly in excess of expenditure. We estimate that an average extra energy intake of 2.8 MJ/day would have had to be consumed for this rise in fat mass to occur even before taking into account the energy intake cost of the rise in expenditure.

Energy expenditure and body composition in growth hormone deficient adults on exogenous growth hormone.

OBJECTIVES: We assessed whether the obesity observed in growth hormone deficient adults is maintained by a reduction in energy expenditure. We studied the effects of exogenous growth hormone on energy expenditure and body composition. DESIGN: We performed an open study with growth hormone administered at 0.5 units per kilogram ideal body weight per week for 3 months. PATIENTS: Seven growth hormone deficient adults were studied. Thirty-eight healthy volunteers had their resting metabolic rate measured, with seven of them proceeding to have their total energy expenditure assessed. MEASUREMENTS: Total energy expenditure was measured by the doubly labelled water method (D2O18), resting metabolic rate by ventilated hood indirect calorimetry, and fat free mass from the dilution volume of oxygen-18. Body composition and components of energy expenditure were assessed before, at 2 weeks and at the end of the 3-month treatment period on exogenous growth hormone. RESULTS: Growth hormone deficient adults did not have a low total energy expenditure compared to healthy controls (13.12 vs 12.75 MJ/24 h) with only one patient expending less than 10 MJ/24 h. None had a resting metabolic rate lower than the 95% confidence limits of normality. The amount of energy expended on physical activity and thermogenesis was significant (6.54 MJ/24 h) and was similar to healthy controls (6.47 MJ/24 h). Resting metabolic rate increased by 15.9% after 14 days on exogenous growth hormone and was elevated 12.1% after 3 months treatment but the ratio to fat-free mass remained unaltered. Total energy expenditure increased by 13.4% after 14 days therapy. Fat-free mass increased significantly after 3 months treatment by (mean) 4.5 kg with no change in fat mass and no loss in body weight. CONCLUSIONS: Obesity maintenance in growth hormone deficient adults is not a consequence of reduced total energy expenditure or a reduced exercise energy output. There was also no evidence for an energy sparing mechanism. Energy expenditure was increased by exogenous growth hormone but was not associated with a loss in fat mass or body weight suggesting the need for dietetic advice for those already obese at the outset of therapy.

Energy expenditure in lean and obese diabetic patients using the doubly labelled water method.

Obesity is a common problem among Type 2 diabetic patients. To investigate the role of energy expenditure in the maintenance of obesity in diabetic subjects, total energy output was measured during weight stability in 23 diabetic patients: 8 lean, 5 overweight, and 10 obese. Free living total energy expenditure was measured over 14 days using doubly labelled water method, resting metabolic rate by indirect calorimetry, and urinary energy losses were assessed. Total energy output was higher in the obese (13.66 +/- SD 3.18 MJ 24 h-1) than normal weight patients (10.84 +/- 2.02 MJ 24 h-1; p < 0.05); 11.96 +/- 2.51 MJ 24 h-1 in the overweight. None of the lean but four of the obese had total energy output > 16 MJ 24 h-1. Urinary energy losses accounted for only 0.6% of total energy output in lean, 2.8% in overweight, and 3.1% in obese. Resting metabolic rate was significantly higher in obese (7.47 +/- 1.69 MJ 24 h-1) compared to lean (5.87 +/- 1.07; p < 0.05) and resting metabolic rate correlated with lean body mass (r = 0.8, p < 0.001). Thermogenesis plus physical activity was substantial and not lower in the obese (5.77 versus lean 4.97 MJ 24 h-1). The mean ratio of total energy expenditure to resting metabolic rate was in the moderate exercise category and similar in lean (1.87) and obese (1.80). Resting metabolic rate, total energy expenditure, and thermogenesis and physical activity were similar in all three groups when corrected for differences in lean body mass.(ABSTRACT TRUNCATED AT 250 WORDS)

The acute effects of corticotropin-releasing factor on energy expenditure in lean and obese women.

Corticotropin-releasing factor (CRF) has been implicated in the development of obesity in genetically obese rodents. We have investigated the effect of 100 micrograms of intravenous CRF on energy expenditure in women, comparing the response in obese and lean volunteers. In response to CRF, energy expenditure as measured by indirect calorimetry increased rapidly with a peak response in both groups reached by two minutes with a ten minute post-CRF response averaging 9.0% in the lean and 11.0% in the obese. Subsequently, energy expenditure remained elevated for a longer duration in the lean compared to the obese. Overall, the total 30 min cumulative metabolic rise was similar in the lean and obese. The increments in energy expenditure were associated with elevation of plasma noradrenaline levels, suggesting the possible involvement of the sympathetic nervous system. The adrenocorticotrophic (ACTH) and cortisol responses to CRF were similar in obese and lean. Intravenous administration of CRF therefore acutely increases energy expenditure in both lean and obese healthy subjects.