Achieving K/DOQI laboratory target values for bone and mineral metabolism: an uphill battle

BACKGROUND: The National Kidney Foundation has recently published the Kidney Disease Outcomes Quality Initiative (K/DOQI) Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease (CKD). According to these guidelines, in patients with stage 5 CKD, the adjusted calcium level should be 8.4- 9.5 mg/dl, the serum phosphate should be 3.5-5.5 mg/dl, the calcium phosphorous product should be <55 mg(2)/dl(2) and the intact parathyroid hormone (PTH) level should be 150-300 pg/ml. METHODS: In order to evaluate our ability to meet these targets, we reviewed laboratory parameters of bone and mineral metabolism of 140 patients over a 6-month period in an inner city hemodialysis unit. Serum calcium and phosphate levels were determined using standard assays and PTH levels were determined using the Nichols Intact PTH assay. RESULTS: We found that the levels of serum calcium and serum phosphorus fell within the range recommended by the K/DOQI guidelines 49 and 36% of the time respectively. 57% of the determinations for calcium x phosphorus product were <55 mg(2)/dl(2). PTH levels were within the recommended values in 20% of the determinations. Only 7% of the determinations met all four criteria simultaneously in spite of meeting other K/DOQI targets such as hematocrit and dialysis adequacy. CONCLUSION: These data indicate that current practice for the management of bone and mineral metabolism in hemodialysis falls far short of meeting the K/DOQI guidelines.     

Detection of C-erb B2 gene amplification in bilharzial associated bladder cancer using fluorescence in situ hybridization

BACKGROUND: Gene amplifications are common events in different tumor types and may confer diagnostic, prognostic, or therapeutic information for patient management. Fluorescence in situ hybridization (FISH) represents a standard methodologic approach for testing for this genetic alteration, as it is rapid, reproducible and extremely reliable in detecting presence of C-erb-B2 gene amplification for clinical utility. PATIENTS AND METHODS: In this study, FISH is used in a series of archival human bilharzial bladder cancer specimens to evaluate for the presence of cerbB-2 gene alterations in the most common malignant tumor in bilharzial endemic areas, e.g., Egypt and some other countries. The study included 40 cases, 30 males and 10 females. Their ages ranged between 30 years and 76 years (median: 51 years). Twenty-one cases had squamous cell carcinoma, 16 had transitional cell carcinoma, two had adenocarcinoma, and one case had undifferentiated carcinoma. RESULTS: Thirteen out of 40 tumor samples (32.5%) show evidence of true C-erb-B2 gene amplification. Of the remaining samples, 24 (60%) show no gene amplification and three (7.5%) fall into the borderline category with a ratio between one and two C-erb-B2 genes/cell relative to chromosome 17 centromeres. No evidence of chromosome 17 polysomy was found in any cases scored as single copy with the C-erb-B2 probe. CONCLUSION: No significant association was found between gene amplification and any of the tested clinicopathologic parameters or tumor recurrence except for tumor grade where higher tumor grades tended to be associated with more C-erb-B2 gene amplification (P = 0.01) thus reflecting more tumor aggressiveness. So, the amplification of C-erb-B2 in bilharzial associated bladder cancer is probably not independently related to clinical outcome of patients.     

Synthesis of pyrido[2,1-c][1,2,4]triazine,1,2,4 triazolo[4,3-a] pyridine and 2-(substituted-pyrazolyl)nicotinonitrile and their effect on Biomphalaria alexandrina snail enzymes

The reaction of 2-hydrazino-4-(4-methoxyphenyl)-6-pheny-nicotinonitrile 3 with halo compounds yielded 4a-c,5,6. Heating 3 with carbon disulphide gave 7-(4-methoxyphenyl)-5-phenyl-3-thioxo-2,3-dihydro [1,2,4-] triazolo [4,3-a] pyridine-8-carboxylic amide 7. The behaviour of 3 towards some alpha,beta-unsaturated nitriles ,ethoxymethylene and ketene dithioacetal derivatives has been investigated, affording 9a-c,11a-c,13a-c,16a,b respectively. The activity of compounds 4a,5,6 and 7 have been investigated as molluscicidal.     

Determination of meloxicam in bulk and pharmaceutical formulations

Three sensitive and reproducible methods for quantitative determination of meloxicam (mel) in pure form and in pharmaceutical formulations are presented. The first method is high performance liquid chromatography by which the drug is determined in the presence of its degradation products over concentration range 100–500 μg ml⁻¹ with mean percentage accuracy 100.13±0.53. The second method is based on measuring the absorbance of the formed neutral complex between basic methylene blue and mel in phosphate buffer (pH 8) at λ=653.5 nm over concentration range 1–5 μg ml⁻¹ with mean percentage accuracy 99.12±1.18. The third method is based on reaction between 2,3-dichloro-5,6-dicyano-p-benzoquinone resulting in the formation of an intense orange red coloured product after heating in a boiling water bath for 5 min. The coloured product exhibits an absorption maximum at 455 nm, over concentration range 40–160 μg ml⁻¹ with mean percentage accuracy 100.53±1.04.     

Regional haemodynamic effects of urocortin in the anaesthetized rat

Urocortin is an endogenous vasodilator peptide that is related to corticotrophin-releasing factor. We examined the haemodynamic effects of urocortin in thiobutabarbital-anaesthetized rats, via the triple-isotope microspheres technique. Urocortin (3 nmol/kg, i.v. bolus) reduced mean arterial pressure (-25 mm Hg) through a decrease in total peripheral resistance (-43%). This was associated with an increase in cardiac output (+24%) and vasodilatation of the following tissues: heart and stomach (approximately 300% of baseline); liver, intestine, caecum/colon, skeletal muscle and skin (approximately 200%); and testes (approximately 150%). Arterial conductances of the kidneys, spleen and brain were unaffected by urocortin. Neither the vehicle (0.9% NaCl) nor a low dose of urocortin (0.3 nmol/kg) altered any measurements. Therefore, urocortin causes generalized vasodilatation as follows: heart and stomach>liver, intestine, caecum/colon, skeletal muscle and skin>testes.     

Synthesis and antimicrobial activity of some new 2-indolinone derived oximes and spiro-isoxazolines

The synthesis and spectral analysis of some new 1,3-dihydro-3-hydroxy-3-[2-hydroxyimino-2-(substituted phenyl)ethyl]-2H-indol-2-ones (21-32) and spiro[3H-indol-3,5'-(4'H)-isoxazol]-2(1H)-ones (33-44) are described. Sixteen of the synthesized compounds were screened in vitro for their growth inhibitory activity against thirteen species of microorganisms, viz, S. aureus, S. epidermidis, S. faecalis, B. subtilis, B. cereus, E. aerogens, E. coli, P. aeruginosa, P. vulgaris, A. baumonia, A. faecalis, C. albicans and S. cervicae. Most of the compounds exhibited significant antimicrobial activity especially the oximes 28 and 29.     

Extruded and protruded lumbar discs: combined clinical, histopathological, histochemical, immunopathological, histochemical, immunopathological and ultrastructural studies.

A total number of selected 252 patients with prolapsed lumbar intervertebral discs (92 extruded and 160 protruded) were operated upon in Neurosurgery Department Zagazig University Hospital during the period extended from January, 1988, to October 1990. In this study we reviewed their clinical and operative data. Surgical biopsies were taken from randomly selected 120 patients of them (50 extruded and 70 protruded discs) and were subjected to histopathological, histochemical and immunopathological studies. Ultrastructural study was performed for randomly selected 14 cases (7 extruded and 7 protruded discs). The results were compared with 7 normal intervertebral discs obtained from these studies showed that there were no differences between extruded and protruded discs at the histochemical level. Cell mediated immunity could be added as a factor in the pathogenesis of the degenerative process that lead to disc prolapse (in 20% of cases with extruded discs and 57.1% of cases with protruded discs). At the ultrastructural level 85.3% of extruded discs were prolapsed nucleus pulposus while 14.7% were prolapsed annulus fibrosus alone or with nucleus pulposus. All protruded discs were prolapsed annulus fibrosus with nucleus pulposus. These findings may have an impact on the management of this common problem.     

Cholinergic mechanisms involved in release and effect of prostaglandin E2 in HCl-stimulated duodenal HCO-3 secretion in the conscious rat

Using a proximal duodenal loop in conscious rats, we investigated interactions between prostaglandin E2 and nicotinic and muscarinic receptor mechanisms previously found to be involved in the duodenal HCO3- response to HCl. In previous studies using the same model, a 5-min perfusion of the duodenal loop with 150 mmol l-1 HCl produced a marked and sustained HCO3- response. In the present study, the identical challenge produced a rapid 20-fold increase in the luminal output of prostaglandin E2 during acid exposure, followed by a sustained more than twofold elevation above the basal level during the 45 min monitored. The prostaglandin synthesis inhibitor indomethacin (4 mg kg-1 i.p.) suppressed the output of prostaglandin E2 during the HCl challenge from 131 +/- 84 to 15.4 +/- 10.0 pmol cm-1 h-1, and in the post-stimulatory period from 17.3 +/- 9.1 to 4.4 +/- 2.2 pmol cm-1 h-1. The nicotinic receptor antagonist hexamethonium (20 mg kg-1 i.v.) had no effect on the output of prostaglandin E2. The muscarinic receptor antagonist atropine (0.5 mg kg-1 s.c.) had no effect on the output of prostaglandin E2 during HCl challenge, but reduced the post-stimulatory output to 7.7 +/- 4.1 pmol cm-1 h-1. Perfusion of the duodenal loop with 0.1 mmol l-1 prostaglandin E2 produced a HCO3- response that was abolished by hexamethonium (20 mg kg-1 i.v.), but not affected by atropine (0.5 mg kg-1 s.c.).(ABSTRACT TRUNCATED AT 250 WORDS)