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Biomedical subjects

G Lama

Publications and source records attributed to G Lama.

At least 19 recordsLinked to original sources
PubMed2002

[Molecular basis of vesicoureteral reflux].

Primary vesico-ureteral reflux (VUR) is a common disorder in children, with an incidence in an unselected population between 0.5-1%. Twenty seven to forty five percent of an affected patient's siblings will have VUR between birth and children of 2 years or younger. VUR is caused by a structural abnormality of the vesico-ureteral junction, characterised by an abnormally short submucosal segment of the ureter or deficiency in the musculature of the intravesical ureter. The etiology of this malformation is currently not well known, but it is probably related to an abnormal development of the ureteral bud. Several genes, such as PAX2 or similar genes, are involved in this development and the interrelationship between these different genes is slowly being unravelled, providing a first insight into the complex molecular cascade directing the embryogenesis of the excretory system. Each gene involved in the development of the excretory system is a potential candidate gene for VUR. Sanyanusin et al. have identified frameshift mutations in exon 5 in PAX2 in several patients with coloboma-ureteric-renal syndrome, which involved VUR as part of the phenotype. In a separate study, linkage to PAX2 was excluded in a three generation pedigree involving individuals with VUR and renal hypoplasia. These results suggest that VUR is a genetic condition, inherited as an autosomal dominant disorder.

Child↗
PubMed2001

Direct effects of GnRH agonists in human hormone-sensitive endometrial cells.

The antiproliferative effect of two GnRH agonists (leuprorelin acetate and triptorelin), alone or combined with tamoxifen (TAM) or medroxyprogesterone acetate (MPA), on human estrogen-sensitive endometrial cancer cells (Ishikawa) was investigated. Although ineffective when tested alone in all the culture conditions used, both analogues counteracted or even suppressed the estrogen-stimulated growth of Ishikawa cells. The antiestrogenic effect of TAM or MPA was not modified by their association with high doses of the GnRH analogues, but low concentrations of triptorelin combined with MPA 10(-7) M determined a reduction in cell numbers which was greater than that obtained with the progestin or the analogue alone. In addition, analogue treatment prevented the estrogen-induced decrease in the level of estrogen receptors. Our data provide evidence that GnRH agonists can directly inhibit estrogen-stimulated endometrial cancer cell growth and suggest that they may interfere with steroid-receptor machinery.

Antineoplastic Agents, Hormonal↗
PubMed2001

Arterial distensibility and ambulatory blood pressure monitoring in young patients with neurofibromatosis type 1.

Vascular disease is an underestimated complication of neurofibromatosis type 1 (NF1). The few studies available on this disease are based on case reports. The purpose of this study was to evaluate the relationship between 24-h systolic blood pressure (SBP) and 24-h heart rate obtained by ambulatory blood pressure monitoring and the carotid femoral pulse wave velocity, a widely used index of arterial distensibility, evaluated with Complior. We studied 64 young NF1 patients and 30 healthy subjects. There was no difference in pulse wave velocity between NF1 patients and healthy subjects. Ten of the NF1 patients showed 24-h SBP or 24-h diastolic blood pressure (DBP) >95th percentile for age and sex. We divided the NF1 group into subgroups: NF1 patients with 24-h SBP and 24-h DBP < or = 95th percentile for age and sex (NF1A group) and NF1 patients with mean SBP or DBP >95th percentile for age and sex (NF1B group). The pulse wave velocity of NF1A and NF1B patients were 6.3 +/- 1 m/sec and 6.4 +/- 1 m/sec, respectively (P = not significant). A significant relationship was found between 24-h SBP, 24-h heart rate, and pulse wave velocity in healthy subjects, but not in all NF1 patients and also between the NF1A and NF1B groups. Distensibility of the central arteries may be altered by various environmental or genetic factors. Thus, genetic determinants may play a role in the response of the large arteries to blood pressure. The recent discovery of neurofibromin in aortic smooth muscle may explain the vascular abnormalities present in NF1 patients. We emphasize the importance of a careful vascular evaluation using a noninvasive method, such as Complior and a periodic ambulatory blood pressure monitoring to detect NF1 patients at high risk of vascular complications.

Adolescent↗
PubMed2001

Effect of placenta growth factor-1 on proliferation and release of nitric oxide, cyclic AMP and cyclic GMP in human epithelial cells expressing the FLT-1 receptor.

We investigated the effect of placenta growth factor-1 (P1GF-1) on cell growth and on the release of nitric oxide (NO), cyclic AMP (cAMP) and cyclic GMP (cGMP) in human malignant epithelial cells. A noteworthy increase in proliferation was induced in choriocarcinoma cells (BeWo) by P1GF-1 treatment, while breast cancer cells (CG-5) were minimally affected. Western blotting and immunocytochemistry demonstrated the expression of the P1GF-1 receptor fms-like tyrosine kinase-1 (Flt-1) in these models. NO was released in the BeWo culture medium as a result of P1GF-1 treatment, with maximal induction occurring after 6 h. Enhanced cAMP levels were observed after 80 min-6 h, while the amounts of cGMP produced were undetectable. In summary, PIGF-1 stimulates the proliferation of cell types that express Flt-1, other than endothelial cells. In BeWo cells, this effect is preceded by the induction of NO and cAMP as probable downstream effectors of Flt-1 activation.

Blotting, Western↗
PubMed2000

Primary vesicoureteric reflux and renal damage in the first year of life.

We retrospectively examined 93 children (47M/46F) with primary vesicoureteric reflux (VUR) followed for a mean period of 3.5 years. They were divided into two groups. Group A included 34 babies (25M/9F) with a prenatal diagnosis of pelvic dilatation. Mean age at presentation was 12 days and no urinary tract infection (UTI) occurred before our first examination. VUR was unilateral in 21 (62%) patients and bilateral in 13 (38%). It was mild (grades I-III) in 12 (25%) refluxing renal units (RRU) and severe (grades IV-V) in 35 (75%). Renal damage (RD) was present, at diagnosis, in 40 (85%) RRU. There was a greater prevalence of abnormal kidneys in male units (88%) than in female units (75%). Group B included 59 infants (22M/37F) less than 1 year old with UTI. The mean age at first examination was 7.6 months. VUR was unilateral in 32 (54%) infants and bilateral in 27 (46%), mild in 60 (70%) RRU and severe in 26 (30%). At diagnosis, 54 (63%) RRU presented RD, which was more common in females (66%) than in males (44%). Our study confirms that primary VUR associated with prenatal hydronephrosis usually affects males and is severe. VUR diagnosed after UTI, instead, is more common in females and is frequently mild. Although in the first type of reflux RD is often present at diagnosis, then probably congenital, it may always progress after UTI; hence the importance of early diagnosis and careful follow-up in each infant with primary VUR.

Female↗
PubMed2000

Diagnosis and follow-up of cystinuria: use of proton magnetic resonance spectroscopy.

Proton Nuclear Magnetic Resonance (NMR) Spectroscopy of urine (as well as of other biological fluids) is a very powerful technique enabling multi-component analysis useful in both diagnosis and follow-up of a wide range of inherited metabolic diseases. Among these pathologies, cystinuria is characterised by accumulation in urine of four dibasic amino acids, namely lysine, arginine, ornithine and cystine; the last one, being only slightly water soluble, generates urolithiasis. The mentioned aminoacids can be detected in the urine NMR spectrum of cystinuric patients, the most abundant being the lysine (5 mM and over are often detected), whose typical signals become very high; arginine and ornithine are also usually detectable, although pathologic concentrations are lower (usually below 2mM). The proposed NMR technique is also suitable in monitoring the therapy with alpha-mercaptopropionylglycine (MPG), providing quantitation of several metabolites of interest in the follow-up of the pathology, like cystine, creatinine and citrate.

Adolescent↗
PubMed2000

Noninvasive evaluation of arterial abnormalities in young patients with neurofibromatosis type 1.

Neurofibromatosis regroups at least two different autosomal dominant genetic disorders: neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). Vascular disease is an underestimated complication of NF1. Few studies are available on this, all based on case reports. Neurofibromin, NF1 protein product, has also been detected in aortic smooth muscle. The purpose of this study was to evaluate the physical properties of the vessels, by measuring the carotid-femoral pulse wave velocity (PWV). This parameter was assessed by the Complior, a new noninvasive, validated device, used to screen a large population. The authors studied 64 neurofibromatosis patients (34 boys and 30 girls) with a mean age of 12 years (range 5-25 years). To investigate the presence of vascular lesions, aortic stiffness was evaluated by carotid-femoral PWV by using an automatic processor (Complior). They compared data from the PWV with a control group (30 healthy children, 17 boys and 13 girls, mean age 11 years, range 5-23 years). The calculated mean PWV in the control group was 6.5 +/- 1.15 m/s. The mean PWV of the 64 young patients with NF1 was 6.3 +/- 1.02 m/s. There was no difference between the two groups (p=0.39). Nevertheless, analysis of the linear regression has shown a linear relationship between systolic blood pressure (SBP) and PWV in the control group, while in NF1 patients this relationship is not present. The authors suggest that the coexistence of different factors, such as intimal proliferation, thinning media, fragmentation of the elastic tissue, irregularity, stenosis and tortuosity of the vessels, dysplasia of the small vessels, that counterbalance PWV, normalize the mean value. They emphasize the importance of a careful vascular evaluation, using noninvasive method, such as Complior. This device is well accepted by NF1 patients.

Adolescent↗
PubMed2000

Enalapril: antiproteinuric effect in children with nephrotic syndrome.

AIM: The present study was designed to establish the antiproteinuric effect of ACE-I (enalapril). PATIENTS AND METHODS: Six children with steroid-resistant nephrotic syndrome (SRNS) and one patient affected by Alport syndrome and nephrotic-range proteinuria received enalapril (mean dose 0.3 mg/kg/day) during a mean period of 2 years. Before initiation of therapy, blood pressure was normal in all but one patient, the latter showed normal values with enalapril treatment. RESULTS: Five patients showed a significant increase of albumin levels after the treatment. Creatinine clearance remained stable during the study in all but one patient affected by Alport syndrome. CONCLUSION: In five patients (71.4%) enalapril therapy resulted in an important reduction ofproteinuria, in one patient the treatment was stopped after one year for relapse. In patient with Alport syndrome the fall in creatinine clearance, may simply reflect the natural course of the disease.

Adolescent↗
PubMed1999

[Chronic renal insufficiency and growth retardation: not an inseparable binomial].

BACKGROUND: The aim of the study was to evaluate, in children with chronic renal failure and in conservative treatment, the degree to which their growth was compromised, in relation with bone age and with GRF. METHODS: The growth of children (12 F, 14 M) with CRI has been evaluated retrospectively in relation to bone age and GFR. Their mean age at diagnosis was 5.8 years. The pathologies-causing CRI were, in particular, congenital anomalies and hereditary nephropathies. The mean follow-up was 6.1 years. RESULTS: No significant difference was found between bone age (BA) and chronologic age (CA) (4.7 +/- 3.4 vs 5.7 +/- 3.5 years, p < 0.3) at diagnosis, while it was lightly delayed (8.6 +/- 5.2 vs 11 +/- 5.6 years, p < 0.07) at the end of the study. At diagnosis the mean height SDS for CA was 0.64 +/- 1.12, at the end of observation was -1.2 +/- 1. Only in 3 patients height was < -2DS: two of them underwent rhGH treatment; the third patient had a growth potential exhausted. The mean height velocity (HV) was 6 +/- 4.2 cm/y at diagnosis and 4.8 +/- 3 at last observation (p < 0.3). No significant difference at diagnosis was found between the HV cm/y and GRF stratified for range, at follow-up there was light significant difference between HV and light CRF vs severe (p < 0.02). Likewise no significant relationship between HV and CA was observed. Actually 20 patients are in conservative treatment, 6 received renal transplantation: for them the growth has been proportional to reached renal function and age of receiver. CONCLUSIONS: The conservative therapeutic regimens and good compliance allowed to limit growth deficiency.

Adolescent↗
PubMed1998

Sensitivity of human melanoma cells to oestrogens, tamoxifen and quercetin: is there any relationship with type I and II oestrogen binding site expression?

We investigated the effect of oestrogens, anti-oestrogens and flavonoids on the growth of a human melanoma cell line (SK-Mel-28) and, at the same time, the presence of both type I oestrogen receptors (ERs) and type II oestrogen binding sites (type II EBS) to gain a fuller picture of the relationship between melanoma cell proliferation and receptor status. 17beta-Oestradiol (E2) and the flavonoid quercetin (Q) produced a marked inhibition of proliferation, but only at the highest dose used (10(-5) M) and only when added daily to the medium. Diethylstilboestrol (DES) (10(-5) M) was effective in inhibiting cell growth when the medium was renewed every 3 days and produced a more pronounced reduction when added daily to the medium. Tamoxifen (TAM) inhibited cell proliferation at a dose starting from 10(-7) M when the medium was renewed every 3 days. When added daily to the medium, it did not induce a greater inhibitory effect and it was cytotoxic at 5 x 10(-6) M and 10(-5) M. The antiproliferative effect of E2, DES and Q did not seem to be dependent on their interaction with ERs, which were minimally detected in SK-Mel-28 in both immunocytochemical and biochemical assays. Our model revealed, through a biochemical assay, a large number of type II EBSs which could be involved in the anti-oestrogen action, but this does not exclude the involvement of other mechanisms. Finally, TAM (10(-5) M) appeared to reduce the activity of the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase, an effect that could be interesting from the point of view of the therapeutic efficacy of alkylating agents.

Anticarcinogenic Agents↗
PubMed1997

Angiotensin converting enzyme inhibitors and reflux nephropathy: 2-year follow-up.

We evaluated the effect of 2 years' therapy with an angiotensin converting enzyme inhibitor (captopril) in 16 patients who had severe reflux nephropathy and microalbuminuria. During the period of therapy, microalbuminuria decreased, glomerular filtration rate measured by diethylenetriamine pentaacetate scan, serum creatinine, and blood pressure remained stable. We suggest the captopril was useful in reducing microalbuminuria and may have slowed the progression of renal damage in our patients.

Adolescent↗
PubMed1997

[Hormone receptors and growth factors in carcinoma of the prostate].

The therapeutic and prognostic significance of androgen receptors in prostatic carcinoma has been examined on the basis of data obtained with the different techniques used in receptor determination. Moreover, the role of some polypeptide growth factors in the regulation of prostatic cancer growth and progression has been reviewed. Great attention has been focused on in vitro models utilized to investigate androgen receptor alterations and the effects of the different positive and negative regulators of prostatic carcinoma cell growth.

Androgens↗
PubMed1996

Combined effects of 13-cis-retinoic acid, tamoxifen and interferon on the growth of human breast cancer cells.

We studied the effect of 13-cis-retinoic acid (13-cRA) alone and in combination with interferons (IFNs) and tamoxifen (TAM) in two established human breast cancer cell lines: the estrogen-sensitive CG-5 and the estrogen-insensitive MDA-MB-453 cells. 13-cRA (10(-9)-10(-5) M) significantly reduced the growth of both cell lines in a dose-dependent fashion, after 3 and 6 days of treatment. When the retinoid (10(-9)-10(-5) M) was combined with natural beta-IFN (100-1000 IU/ml) for 6 days, we observed a growth inhibition more pronounced than that produced by each of the two single agents in both CG-5 and MDA-MB-453 cells. Only in the former model was the inhibitory effect synergistic at all the drug concentrations used. Association of 13-cRA (10(-9)-10(-5) M) and recombinant alpha2a-IFN (100-1000 IU/ml) or TAM (10(-7)-10(-6) M) did not determine an additive or synergistic effect on the growth of CG-5 cells.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[Risk factors in calcium urolithiasis].

The aim of the study has been to evaluate, retrospectively, if the association of urolithiasis different pathogenetic factors increases stone formation and recurrences. The study included 41 children, 20 males and 21 females, aged 3-15 years, divided into three groups: patients with hypercalciuric or normocalciuric urolithiasis and isolated hypercalciuria. In all of them renal function, blood and urinary pH, serum and urinary electrolytic levels, citraturia (dosed with anenzymatic quantitative method), oxalaturia (enzymatic colorimetric method), urinary glycosaminoglycans (dosed by means of cetylpyridinum chloride precipitation and quantitative analysis) have been considered. Statistical analysis was done using Student's "t"-test, with p < 0.05. In all children with hypercalciuric urolithiasis who during the follow-up presented a decreased citraturia, the number of recurrences increased and was above two. The children who during the follow-up remained hypercalciuric without urolithiasis, in spite of the high familiarity, presented an increased citraturia. In conclusion the association between hypercalciuria and low citraturia increases the risk of stone formation and recurrences in children with calcic urolithiasis.

Adolescent↗
PubMed1995

Spondyloepiphyseal dysplasia tarda and nephrotic syndrome in three siblings.

The association of a spondyloepiphyseal dysplasia tarda (SED-T) with the nephrotic syndrome (NS) was found in three siblings. They have counsaguineous (first cousins) healthy parents. Patient 1 was a boy who was admitted to hospital for oedema at the age of 8 years; NS was diagnosed, renal biopsy revealed mesangioproliferative glomerulonephritis. After 4 years he developed end-stage renal failure and died whilst on haemodialysis. Combined therapy with cyclophosphamide and prednisone was of no benefit. At the age of 11 years his height was 122 cm (< 3rd percentile -3.2 SD); he had a short neck, broad and prominent chest and a short wide trunk. Patient 2, another male, had non-nephrotic proteinuria in a 24-h urinary sample at the age of 11 years; this was confirmed in a later analysis; mild lymphopenia and a reduction of helper T cell (OKT4)/suppressor T cell (OKT8) ratio was also detected. At 22 years of age he was admitted to hospital with end-stage renal failure. He was on haemodialysis for a few months until his mother donated a kidney. At the age of 22 years his height was 157 cm (< 3rd percentile), he had a short trunk with the thoracic cage increased in anteroposterior diameter and shoulder elevation. Roentgenograms revealed a disostosis of the spinal column and pelvis and a slight lombar platyspondylia. Patient 3, a girl, was admitted to hospital at 12.5 years for pain and restricted mobility of the right hip. X-rays showed deep acetabula and short femoral necks and mild dysplastic changes, especially in the right hip.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Natural interferon-beta treatment and steroid hormone receptors in primary endometrial cancer.

Forty-three patients with primary endometrial carcinoma were treated with natural interferon-beta (IFN-beta) at two different dose levels (2 x 10(6) IU or 6 x 10(6) IU im 3 times/week for 1 week). IFN-beta increased receptors for estrogens (ER) and progesterone (PR) in a high percentage of the 40 evaluable patients, without modifying the receptor affinity. The ER and PR enhancement, which was simultaneous in at least 50% of patients, and the increase of over 100 fmol/mg protein observed in some cases suggest that IFN-beta exerts a profound influence on receptor expression and, probably, on the hormone sensitivity of the tumor.

Adenocarcinoma↗