Protein metabolism in patients with chronic renal failure: role of uremia and dialysis

Individuals with chronic renal failure (CRF) have a high prevalence of protein-energy malnutrition. There are many causes for this condition, chief among which is probably reduced nutrient intake from anorexia. In nondialyzed patients with CRF, energy intake is often below the recommended amounts; in maintenance dialysis patients, both dietary protein and energy intake are often below their needs. Although a number of studies indicate that rats with CRF have increased protein catabolism in comparison to control animals, more recent evidence suggests that increased catabolism in CRF rats is largely if not entirely due to acidemia, particularly if these animals are compared to pair-fed control rats. Studies in humans with advanced CRF also indicate that acidemia can cause protein catabolism. Indeed, nitrogen balance studies and amino acid uptake and release and isotopic kinetic studies indicate that in nondialyzed individuals with CRF, who are not acidemic, both their ability to conserve body protein when they ingest low protein diets and their dietary protein requirements appear to be normal. For patients undergoing maintenance hemodialysis or chronic peritoneal dialysis, dietary protein requirements appear to be increased. The increased need for protein is due, in part, to the losses into dialysate of such biologically valuable nitrogenous compounds as amino acids, peptides, and proteins. However, the sum of the dietary protein needs for CRF patients (of about 0.60 g/kg/day) and the dialysis losses of amino acids, peptides and proteins do not equal the apparent dietary protein requirements for most maintenance dialysis patients. This discrepancy may be due to a chronic state of catabolism in the clinically stable maintenance dialysis patient that is not present in the clinically stable nondialyzed individual who has advanced CRF. Possible causes for such a low grade catabolic state include resistance to anabolic hormones (for example, insulin, IGF-1) and a chronic inflammatory state associated with increased levels of pro-inflammatory cytokines.     

A man with osteoblastic metastasis and hypocalcaemia

We report a case of an 80-year-old man with osteoblastic metastases from advanced carcinoma of the prostate presenting with a grand mal seizure resulting from severe hypocalcaemia. He had low serum phosphate and ionised calcium levels, elevated serum skeletal alkaline phosphatase and intact parathormone levels. 99mTc radioisotope bone scan revealed a "super bone scan" suggestive of osteomalacia. The serum 1, 25-dihydroxycholecalciferol level was unexpectedly elevated. The biochemical abnormalities persisted despite high dose calcium replacement, but improved with supraphysiological doses of 1,25 (OH)2 vitamin D3 (Rocaltrol) therapy. We hypothesise that the hypocalcaemia in this patient was due to vitamin D resistance secondary to a humoral factor secreted by the tumour.     

Reduced levels of growth hormone, insulin-like growth factor-I and binding protein-3 in patients with shunted hydrocephalus

OBJECTIVE: Children with hydrocephalus are characterised by slow linear growth in prepuberty, accelerated physical maturation during puberty, and reduced final height. We aimed to study the possible roles of growth hormone, insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3) in this growth pattern. STUDY DESIGN: One hundred and fourteen patients with shunted hydrocephalus (62 males) aged 5 to 20 years, of whom 17 had spina bifida (six males), and 73 healthy controls (38 males) were studied. Anthropometric measures, body mass index, and body fat mass were assessed and the stage of puberty was determined. Serum growth hormone and plasma IGF-I and IGFBP-3 concentrations were measured. RESULTS: The patients comprised 44 (26 males) who were prepubertal and 70 (36 males) pubertal or postpubertal, while 32 of the controls (19 males) were prepubertal and 41 (19 males) pubertal or postpubertal. The prepubertal children with hydrocephalus had lower IGF-I (p = 0.002) and IGFBP-3 concentrations (p < 0.001) than the controls, and the pubertal children had four times lower basal growth hormone concentrations (p < 0.001). There was a correlation between height SD score and IGF-I levels in the total patient population (r = 0.23; p = 0.01). Peripheral IGF-I concentrations peaked at pubertal stages 2-3 in the female patients and at stage 4 in the controls. The prepubertal patients on antiepileptic treatment, carbamazepine in most cases (73%), had higher IGF-I (p = 0.01) and IGFBP-3 concentrations (p = 0.03) than those who had never been treated with antiepileptic drugs, but still lower IGFBP-3 levels than the controls (p = 0.01). CONCLUSION: Based on these findings, it can be concluded that reduced growth hormone secretion may contribute to the pattern of slow linear growth and reduced final height observed in these patients.     

Validity and cost-effectiveness of diagnostic procedures in CS2 poisoning

To determine relatively useful diagnostic procedures of carbon disulfide (CS2) poisoning in terms of validity and cost-effectiveness, several diagnostic tests are evaluated on 1,552 people by prevalence ratio (exposed/nonexposed), dose-response relationship, sensitivity and specificity, and the cost of the tests. Several symptoms with high kappa indices are found to be useful in various combinations, showing a consistent dose-response relationship and high exposed-nonexposed ratio. In clinicopathologic tests on functions of the kidney, liver and hematopoietic systems, eight items out of 22 have been shown to have significant dose-response relationship, mostly in liver function tests. A thorough dental examination failed to identify any useful indicator peculiar to the CS2 poisoning. Unlike Western people, the prevalence of coronary heart disease among Koreans was too low to be useful in the diagnosis of CS2 poisoning. Among four elective tests, i.e., Minnesota Multiphasic Personality Inventory (MMPI), Brain magnetic resonance imaging (MRI), nerve conduction velocity (NCV), and fluorescent angiography (FAG), the NCV appeared to be a more sensitive and specific test than the others are. Combinations of the tests improved the probability of diagnosing CS2 poisoning cases when any one test out of four was positive. Addition of other valid tests increased the probability of excluding non-cases. It was concluded that diagnosis of CS2 poisoning could be made validly and inexpensively if the diagnostic tests were carefully chosen step by step.     

Chronic (-)-hydroxycitrate administration spares carbohydrate utilization and promotes lipid oxidation during exercise in mice

(-)-Hydroxycitrate (HCA) is an active ingredient that is extracted from the rind of the Indian fruit, Garcinia cambogia, which is available as an herbal supplement and is used to lose weight. In this study, the acute and chronic effects of HCA on energy metabolism were examined in male Std ddY mice. Mice were placed into metabolic chambers and administered 10 mg HCA or water (control) orally. Serum free fatty acid levels were significantly higher 100 min after administration in the HCA group, but the respiratory exchange ratio was not different from that in the control group. The concentration of glycogen in the gastrocnemius muscle was higher in the HCA group 16 h after administration, and in a separate study, the maximum swimming time until fatigue was slightly longer (P: = 0. 21) than that in the control group on d 1. The difference was significant on d 3 after 3 d of HCA or water administration. Other mice were administered 10 mg HCA or water orally twice a day for 25 d. On d 26, they were placed into metabolic chambers after administration and allowed to rest for 1 h, followed by 1 h of running at 15 m/min. Respiratory gas was monitored. The respiratory exchange ratio was significantly lower in the HCA group during both resting and exercising conditions. These results suggest that chronic administration of HCA promotes lipid oxidation and spares carbohydrate utilization in mice at rest and during running.     

A randomised trial of amoxycillin versus clarithromycin in combination with omeprazole for eradication of Helicobacter pylori infection in Singapore

Dual therapy has been reported to produce H.pylori eradication rate of 75-80%. This study is designed to determine the efficacy of omeprazole 20 mg bd in combination with amoxycillin 500 mg tid (Group A), amoxycillin 750 mg tds (Group B) and clarithromycin 500 mg tid (Group C) in Singapore. One hundred and forty-eight patients with H. pylori positive duodenal ulcers between ages of 22 and 69 were enrolled from two centres. There were 48 patients in Group A, 50 patients in Group B and 50 patients in Group C. The medication was given for 14 days. The patients were re-evaluated with an upper GI endoscope 4 weeks after cessation of treatment Successful eradication was defined as H.pylori negative on histology and culture. Based on intention to treat analysis, the eradication rate was 47.8% in Group A, 68% in Group B and 66% in Group C. The difference between GroupA and B were statistically significant (p = 0.04). Based on all patient treated analysis, the eradication rate was 57.5% in Group A, 70.7% in Group B and 75% in Group C. The difference in eradication rates was not statistically significant. Adverse events were reported in 21% of all patients with no difference in the adverse event rate between all groups. The eradication rate achieved with dual therapy in this study was similar to that attained in Western population. Higher dose amoxycillin regime gives a significantly higher eradication than a lower dose amoxycillin.     

Giant cell arteritis causing bilateral sequential anterior ischaemic optic neuropathy--a case report

Giant cell arteritis is a chronic granulomatous inflammation of unknown aetiology involving large and medium size arteries in the elderly. It causes acute visual loss from ischaemia to the optic nerves or central retinal artery occlusion. This is a rare cause of anterior ischaemic optic neuropathy in our local population. We present a patient who had bilateral loss of vision from sequential arteritic ischaemic optic neuropathy. She was treated with intravenous steroids immediately. Diagnosis was based on histopathological studies of temporal artery biopsies.     

Increasing breastfeeding rates to reduce infant illness at the community level

OBJECTIVE: Although breastfeeding is associated with lower rates of a variety of infant illnesses, skeptics have suggested that much of the association is attributable to confounding, even after appropriate statistical adjustment. This article utilizes a novel design to investigate changes in infant illness at the community level after a successful breastfeeding promotion program. METHODS: In this population-based cohort study, the medical records of all infants born in one Navajo community the year before a breastfeeding promotion program (n = 977) and the year during the intervention (n = 858) were reviewed. Outcomes assessed include changes after the intervention in: proportion breastfeeding and/or breastfeeding exclusively; incidence of common infant illnesses in the first year of life; and feeding-group specific incidence of illness. RESULTS: The proportion of women breastfeeding exclusively for any period of time increased from 16.4% to 54.6% after the intervention. The percent of children having pneumonia and gastroenteritis declined 32. 2% and 14.6%, respectively, after the intervention. Feeding-group specific rates of these illnesses were unchanged, indicating that the decline observed was attributable to the increased proportion of infants breastfeeding. In contrast, rates of croup and bronchiolitis increased after the intervention among those fed formula from birth, suggesting a viral epidemic which was limited to those never exclusively breastfed. Finally, sepsis declined in both formula-fed and breastfed infants after the intervention, suggesting that other factors affected this illness outcome after the intervention. CONCLUSIONS: Increasing the proportion of exclusively breastfed infants seems to be an effective means of reducing infant illness at the community level. The experimental design suggests that the increased incidence of illness among minimally breastfed infants is causally related to lack of breast milk, rather than being attributable to confounding.     

Stated and actual management of acute myocardial infarction among different specialties

OBJECTIVES: To examine the variation in stated management of acute myocardial infarction (AMI) among clinicians of different specialties, and to compare stated with actual practice. DESIGN: Mail survey using a hypothetical case history, and review of medical records. SETTING: 47 public hospitals in New South Wales. SUBJECTS: 224 cardiologists, general/other physicians and general practitioners (GPs) who manage patients with AMI; 390 patients admitted for AMI between February and June 1996. OUTCOME MEASURES: Stated and actual use of treatments and investigations for AMI. RESULTS: Stated use of aspirin, thrombolysis and beta-blockers (95%-100%, 95%-100% and 80%-86%, respectively) was high in all three specialties. Cardiologists were significantly more likely than GPs to state use of heparin (87% v 57%; P < 0.001), ACE inhibitors (84% v 49%; P < 0.001) and echocardiography or gated pool heart scan (79% v 26%; P < 0.001). Stated use of nitrates by cardiologists was significantly lower compared with the other specialties (29% v 50% and 44%; P = 0.027). Actual use of aspirin was high (> 80%) in all specialties. Actual use of thrombolysis was similar to stated use after adjusting for factors such as time to hospital arrival and ST-segment elevation. There were substantial differences between stated and actual use. CONCLUSIONS: There were differences in practice patterns between and among clinicians of different specialties in NSW, consistent with findings from other countries. The high stated and actual use of aspirin and thrombolysis is encouraging.