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Biomedical subjects

G Gambaro

Publications and source records attributed to G Gambaro.

At least 127 records · Page 7Linked to original sources
PubMed1984

[Role of Tamm-Horsfall mucoprotein in calcium oxalate lithogenesis].

Tamm-Horsfall (TH) mucoprotein has been suggested to play a lithogenetic role in calcium-oxalate nephrolithiasis. However it is still debated whether it promotes or inhibits crystal growth and aggregation. To make clear the role played by this mucoprotein, we have carried out the following experiments: 1) the urinary excretion of TH has been evaluated by radial immunodiffusion in 27 recurrent idiopathic CaOx stone formers and in 35 controls; 2) in a metastable solution of CaOx the effect of TH addition on crystal growth has been monitored; 3) in whole urine the effect of TH addition on crystal aggregation has been assayed by an aggregometer. Urinary excretion of TH is significantly lower in stone formers. TH does not seem to promote crystal growth, while it is effective on crystal aggregation. These data seem to suggest that the reduced excretion of TH in nephrolithiasis may be a lithogenic risk factor.

Calcium Oxalate↗
PubMed1984

[Abnormalities in the erythrocyte membrane transport of oxalate in calcium oxalate lithogenesis].

The high incidence of a family history and the observation of abnormally high intestinal absorption and urinary excretion of oxalate suggest to consider idiopathic calcium oxalate nephrolithiasis as a metabolic disease characterized by a disorder in oxalate transport. To test this hypothesis, the flux of 14C Oxalate through the membrane of red blood cells was investigated in 24 calcium oxalate stone formers; 18 of the 24 "idiopathic" calcium oxalate stone formers showed an increased oxalate self exchange (75%). Our data seem to support the possibility that "idiopathic" calcium oxalate nephrolithiasis may be considered as a metabolic disease marked by a defect in transmembrane transport of oxalate.

Adult↗
PubMed1983

Juvenile renal stone disease: a study of urinary promoting and inhibiting factors.

Urinary excretion of the most widely studied renal stone promoting (calcium, oxalate, uric acid and phosphate) and inhibiting (citrate, magnesium, pyrophosphate and glycosaminoglycans) factors, as well as the Tamm-Horsfall mucoprotein, was evaluated in 14 children with idiopathic calcium nephrolithiasis, 6 children with renal stone disease secondary to excretory malformations and 19 normal controls. No statistically significant differences in urinary excretion of promoting and inhibiting factors were found in children with idiopathic calcium nephrolithiasis but the relationship between promoting and inhibiting factors was changed as shown by an abnormal ratio of oxalate/citrate X glycosaminoglycans. This finding suggests that there is an imbalance between promoting and inhibiting factors in children with idiopathic calcium nephrolithiasis, and it is not detected by assay of each single substance.

Adolescent↗
PubMed1983

Increased urinary excretion of renal enzymes in idiopathic calcium oxalate nephrolithiasis.

Urinary excretion of gamma-glutamyl transpeptidase, angiotensin I converting enzyme, beta-galactosidase and N-acetyl-beta-glucosaminidase was evaluated in 30 patients with idiopathic calcium oxalate urolithiasis. Higher than normal values were observed and the excretory enzyme pattern suggested tubular damage in patients with stones. A parallel study in the rat showed that an oxalate surcharge can promote increased urinary excretion of these enzymes. It is known that urothelium injury may enhance crystal adhesion. If the damage is primary it may be viewed as a promoting factor. If it is secondary it may be considered a factor capable of increasing salt precipitation.

Acetylglucosaminidase↗
PubMed1983

Prevalence of hyperoxaluria in idiopathic calcium oxalate kidney stone disease.

Urinary excretion of oxalate, calcium and urate has been investigated in 88 patients affected by idiopathic calcium oxalate stone disease and in 20 normal subjects. Of these ions, only oxalate was found significantly higher in stone formers. Defining hyperoxaluria as urinary oxalate excretion greater than 2 SD above normal, 50% of stone-forming people were found to be hyperoxaluric. When stone formers were classified in normo- and hyperoxaluric, the prevalence of hypercalciuria, hyperuricuria, family history of stone disease and recurrencies in stone formation was the same in both groups. It is concluded that hyperoxaluria is a frequent finding in finding in idiopathic calcium oxalate renal stone disease.

Adult↗
PubMed1982

Calcium oxalate nephrolithiasis: an easy way to detect an imbalance between promoting and inhibiting factors.

Calcium oxalate stone formation depends on both urine oversaturation with calcium oxalate--which in turn depends mainly on oxalate excretion--and the excretion of inhibitors; the possibility that a ratio of these variables might differentiate stone-formers from stone-free subjects was explored, 24-h urine samples from 20 control subjects and 53 idiopathic calcium oxalate stone-formers receiving a standard diet were studied. A further group of 2-h urine samples (from 7 to 9 a.m.). collected after a overnight fast from 16 non-stone and 24 stone-forming persons on a normal diet, were also examined. The ratio 'oxalate/citrate X acid mucopolysaccharides; (Ox/Cit X AMPs) seems capable of differentiating more than 80% of stone-formers from non-stone-formers using both 24- and 2-h urine collection.

Adult↗
PubMedDate not supplied

Vascular endothelial growth factor (VEGF) and VEGF receptors in diabetic nephropathy: expression studies in biopsies of type 2 diabetic patients.

Vascular endothelial growth factor (VEGF) is involved in the pathogenesis of diabetic retinopathy but its role in diabetic nephropathy is only speculative so far. It has been shown that in renal cortex of normal kidneys, glomerular and tubular epithelial cells express VEGF and that VEGF 165 is the predominant isoform. Two VEGF receptors, KDR (kinase domain region) and Flt-1 (fms-like tyrosine kinase) are co-expressed by glomerular and peritubular capillary endothelial cells. However, VEGF and VEGF receptors are predominantly expressed at glomerular level. We recently demonstrated that in type 2 diabetic patients glomerular qualitative and quantitative changes of VEGF mRNA expression are associated with functional and structural renal changes. In the present work we focused on the tubulo-interstitial compartment; by reverse transcription/polymerase chain reaction (RT/PCR) we evaluated the expression of VEGF, KDR, Flt-1 and the relationship between the two main type of VEGF isoforms, VEGF121 and VEGF165 in the tubulo-interstitium of type 2 diabetic patients. Patients were divided in three category on the basis of renal structure pattern: CI, with normal or near normal renal structure; CII, with glomerular and tubulo-interstitial lesions occurring in parallel (typical diabetic nephropathology); CIII, with atypical pattern of renal injury, i.e., more severe tubulo-interstitial and vascular than glomerular changes. Comparison between the two cortical compartments revealed that, both in glomeruli and in tubulo-interstitium. VEGF121 isoform exceed VEGF165 while Flt-1 was significantly lower in glomeruli. CIII patients had the lowest tubulo-interstitial level of VEGF and Flt-1 mRNAs. These results suggest that the transcriptional shifting from VEGF165 to VEGF121 isoform and the unbalanced FIt-1 expression between tubulo-interstitium and glomeruli could be involved in the pathogenesis of diabetic nephropathy. Furthermore, at least in CIII patients, down-regulation of the VEGF-Flt-1 system could be involved in the mechanisms leading to tubulointerstitial diabetic lesions.

Adult↗
PubMedDate not supplied

A comparative kinetic RT/-PCR strategy for the quantitation of mRNAs in microdissected human renal biopsy specimens.

Molecular biology techniques, to be applicable to a diagnostic renal biopsy specimen, should (1) be highly sensitive to be performed on a very small quantity of tissue; (2) be quantitative because they have to analyze genes normally expressed in the tissue and (3) allow the analysis of as large a number of genes as possible. Among different methods, only the reverse-transcriptase polymerase chain reaction (RT/-PCR) might comply with previous requisites, but the few RT/-PCR examples on renal biopsies in the literature do not allow starting RNA quantification and quality control; furthermore they have the drawback of analyzing only few genes. In an ongoing study to assess the expression of a number of genes in glomeruli and in tubulointerstitium of patients with different nephropathies, we developed a comparative RT/-PCR kinetic strategy based on the purification and quantification of total glomerular and tubulointerstitial RNA and on the use of an internal standard, the housekeeping gene G3PDH. We demonstrate that in microdissected diagnostic renal biopsies (1) glomerular and interstitial starting RNA can be quantified; (2) the G3PDH gene may be used both as an internal standard and as an indirect marker of RNA integrity; (3) as low as 28 ng of total RNA is sufficient to obtain PCR products of eight genes, and (4) it is worth to operate on microdissected biopsy specimens because of the different expression of genes in the two renal compartments.

Actins↗
PubMedDate not supplied

Azelastine in the prophylactic treatment of bronchial asthma: an Italian multicentre comparison with ketotifen.

The prophylactic effectiveness of the phthalazinone derivative, azelastine was compared with ketotifen. A total of 111 patients, aged 18-65 years, from 10 centres was entered into this randomized, double-blind study. All patients had reversible asthma. After 1 week on placebo, patients were allocated to either 8 mg/day azelastine once or twice daily, or to 1 mg ketotifen, twice daily, for a further 12 weeks. Azelastine was more effective in improving respiratory function (forced expiratory flow in 1 s and peak expiratory flow rate) when given in the once daily regimen, whereas clinical measures (number of weekly asthma attacks) were most improved by twice daily dosing. There was no significant difference between the effectiveness of azelastine and that of ketotifen. Treatments were equally well tolerated and a low incidence of side-effects was reported. In conclusion, 8 mg/day azelastine, in either a single or twice daily dosage regimen may be regarded as providing effective prophylaxis against bronchial asthma.

Adult↗
PubMedDate not supplied

Concurrent chemotherapy with carboplatin + 5-fluorouracil and radiotherapy in advanced squamous cell head and neck carcinoma: a retrospective single institution's study.

AIMS AND BACKGROUND: [corrected] The purpose of the study was to analyze the long-term follow-up of a single institution's experience with a regimen of concomitant carboplatin + 5-fluorouracil (CBDCA + 5-FU) infusion and radiotherapy. STUDY DESIGN: Fifty-eight patients with locally advanced squamous cell head and neck cancer treated with combined chemoradiotherapy between March 1990 and October 1998 were reviewed retrospectively. According to the TNM tumor staging, 6 patients had stage II, 21 stage III and 31 stage IV tumors. The chemotherapy regimen consisted of the combination of 5-FU and CBDCA, for a total of 3 cycles. Both drugs were given as 4-day continuous intravenous infusions during the first and fourth week of radiation therapy: 5-FU at 1000 mg/m2 per day and CBDCA at 75 mg/m2 per day. Radiation was given in single daily fractions of 1.8 to 2 Gy, to a total dose of 66 to 70 Gy. RESULTS: After the completion of chemotherapy and radiotherapy, 34 patients (58.6%) achieved clinical and radiological (computerized tomography and/or magnetic resonance imaging) complete remission, 15 patients (25.9%) partial remission >50%, 5 patients (8.6%) partial remission <50%, and 4 patients (6.8%) had no response. Toxicity was intensive but tolerable. After a median follow-up of 25 months, overall survival and recurrence-free survival estimated for the whole patient population was 52% at 3 years, and the median length of recurrence-free survival was 23 months. CONCLUSIONS: Our regimen combining standard single daily fraction radiation with the conventional dose of CBDCA and 5-FU was given without dose modification regardless of the severity of the adverse effects. It gave a clinical complete response at the primary site in 58.6% of patients. With a 52% projected 3-year overall survival, our series compares favorably with similar studies in the literature. Therefore, our results with concomitant CBDCA/5-FU infusion and radiotherapy are encouraging and suggest that CBDCA can be substituted for cisplatin with a good therapeutic index.

Adult↗
PubMedDate not supplied

[Gout and kidney during XVII and XIX centuries].

The authors briefly describe the history of gout, mainly focusing their attention on the renal involvement. They report some works and theories on gout of great ancient physicians, such as Paracelsus, Sydenham, Boerhaave, Van Swieten and Morgagni.

Europe↗
PubMedDate not supplied

Renal involvement in subjects with peripheral atherosclerosis.

BACKGROUND: Ischemic nephropathy is an important cause of renal failure in western countries. Subclinical renal function abnormalities may exist in patients with extrarenal atherosclerosis, and may precede the onset of overt ischemic nephropathy. METHODS: To assess the impact of extrarenal atherosclerosis on the kidney, we evaluated renal function in 89 subjects with differing degrees of peripheral atherosclerosis, without manifest clinical or laboratory signs of ischemic nephropathy and renovascular hypertension. All laboratory testing, ultrasonography with Doppler analysis for the localization of peripheral vascular disease (carotid and lower limb arteries), and non-invasive evaluation of renal function by radionuclide studies of renal plasma flow (MAG3 clearance) and glomerular filtration (DTPA clearance), as well as total, LDL and HDL cholesterol, and triglycerides were determined; smoking habit was recorded. By combining sonographic data on arterial tree stenosis (ATS), the subjects were grouped according to the atherosclerotic vascular damage (ATS involvement). RESULTS: Despite no change in plasma creatinine and DTPA clearance (from 91.58+/-26.53 mL/min/1.73 m2 to 93.47+/-24.82), MAG3 clearance progressively declined with the severity of vascular damage (from 244.86+/-60.60 mL/min/1.73 m2 to 173.59+/-58.74). Stepwise multiple regression analysis indicated that MAG3 clearance was best explained by ATS involvement (standardized beta coefficient -0.40; p<0.001), smoking habit (-0.34; p= 0.004), and serum LDL-cholesterol (-0.24; p<0.035). CONCLUSIONS: The renal hemodynamic profile in atherosclerotic patients might constitute functional evidence of the silent phase of ischemic renal disease. The findings suggest that renal function should be carefully assessed in patients with extrarenal atherosclerosis, particularly in those with classic cardiovascular risk factors.

Aged↗
PubMedDate not supplied

[In search of renal stem cells].

The therapeutic potential of stem cell research is very promising. Although arising ethical questions, especially in the field of embryonic stem cells (ES), it is astonishing how, in the last few years, the potential application of stem cells for treating proliferative as well as degenerative diseases, is becoming increasingly evident. It was recently demonstrated that somatic stem cells showed unexpected plasticity similar to ES. In fact, if somatic stem cells are exposed to proper stimuli they can differentiate into a multitude of cell types that may be different from those of the tissue they belong to. In addition, it was recently demonstrated that circulating blood stem cells, probably of bone marrow origin, were recruited at the sites of injury to regenerate or repair damaged tissues. Very little is known about renal stem cells. Although the great capacity of the kidney to regenerate injured nephrons is well established, renal somatic stem cells have yet to be identified. The question we are now faced with is whether renal stem cells exist and, if they do exist, where do they reside. In the attempt to answer this question, the present review will focus on the achievements both in the fields of somatic stem cells and renal embryogenesis and in the field of renal repair and regeneration mechanisms.

Humans↗
PubMedDate not supplied

[Dent's disease: hereditary nephrolithiasis related to defective tubular endocytosis processes].

Dent's disease, a X-linked hypercalciuric nephrolithiasis, is caused by mutations of the CLCN5 gene. The disease is characterised by low molecular weight proteinuria with variable presence of hypercalciuria, hyperphosphaturia, nephrocalcinosis, and kidney stones. CLCN5 encodes a chloride channel belonging to the voltage-gated chloride channel family, which is predominantly expressed in the endosomes of proximal tubular cells. By shunting the current of electrogenic H+-ATPase, ClC-5 is crucial for efficient acidification of renal endosomes. As shown in knock-out mouse models, the ClC-5 loss of function causes severe impairment of receptor-mediated endocytosis, as well as the endocytotic retrieval of plasma membrane proteins including megalin. In a minority of patients with classical Dent's disease, the analysis of CLCN5 coding sequences failed to identify causative mutations. It is conceivable that mutations in the 5' upstream regulatory regions could impair the correct processing and translation of CLCN5. The complexity of its promoter region seems to support this hypothesis. Molecular diagnosis of Dent's disease is now available; since the risk of developing renal insufficiency in adult life is elevated for this type of nephrolithiasis, the correct diagnosis could potentially modify the natural history of the disease by preventing the evolution towards uraemia.

Animals↗
PubMedDate not supplied

The Leclercq test in diagnosis of tear in the rotator cuff.

The authors report their experience in using the Leclercq test to diagnose tear in the rotator cuff of the shoulder. When positive, this test consists in a radiographic demonstration of reduction in the subacromial space in opposing abduction of the shoulder. Twenty-five patients affected with chronic painful shoulder and suspected lesion of the rotator cuff were submitted to the Leclercq test and subsequently to arthrography in order to evaluate the conditions of the cuff. In all of the cases where the cuff was whole, and arthrography normal, the Leclercq test was negative. When lesion of the cuff was revealed by arthrography, the test was positive in 75% of the cases considered globally, and in 92% of the cases with complete tear in the rotator cuff.

Adult↗