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.     

Radiation Therapy Results for Patients Undergoing Inappropriate Surgery in the Presence of Invasive Cervical Carcinoma

Total vaginal or abdominal hysterectomy was considered an inadequate treatment method for invasive uterine cervix cancer. Usually the procedure was inadvertently performed on patients who were thought preoperatively to have benign or premalignant conditions. Between 1985 and 1993, 64 patients undergoing hysterectomy in the presence of invasive cervical cancer were treated with external radiation therapy and/or intracavitary radiotherapy. Preoperative diagnoses were carcinomain situ(36), severe dysplasia (2), and early invasive cancer (14), and others were benign disease. Overall 5-year survival and relapse-free survival rates were 75.8 and 77.5%, respectively. For patients in retrospective stage IA, IB, and IIB (gross residual after surgery), overall 5-year survival rates were 90.9, 88.8, and 27.9%, respectively. Thirteen patients developed treatment failure; most of them (10/13) were patients with gross residual disease. Patients with early invasive cervical cancer (stage IA) had no treatment-related failure. Prognostic factors affecting survival by univariate analysis were retrospective stage (P= 0.0000) and preoperative diagnosis (P= 0.0021). Tumor histology was marginally significant factor (P= 0.0938). By multivariate analysis, only retrospective stage was significant prognostic factor (P= 0.0001). Adjuvant radiotherapy appears to be an effective treatment method for patients with presumed stage IA and IB after inadvertent hysterectomy. Survival for patients with gross disease remaining after inappropriate hysterectomy is poor. So, early cancer detection and proper management with precise pretreatment staging is necessary to avoid inadherent hysterectomy, especially in cases of gross residual disease.     

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.     

Sequential production and activation of matrix-metalloproteinase-9 (MMP-9) with breast cancer progression

The degradation of the basement membrane by matrix-metalloproteinase(MMP) and serine protease is a critical pointin tumor invasion and metastasis. We measured theactivity of MMP-9 from 28 normal, 12 benignand 126 breast cancer tissues using gelatin zymographywith an image analysis system. ProMMP-9 was expressedin 17.5% of the cancer patients compared to2.5% in 40 non-cancerous tissues (p=0.014).The mature form of MMP-9 (82 kD) wasexpressed only in T2–T4 stages. During the earlyphase of breast cancer (DCIS and T1 stage)progression, only production of proMMP-9 increased. However, asthe cancer grew or invaded skin (T2–T4), orwith lymphovascular permeation, both production and activation ofMMP-9 increased. In conclusion, proMMP-9 production was themain cause of increased MMP-9 activity during theearly phase, while both production and activation increasedin the late phase of breast cancer.     

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.