Search PubMed⌕ Search

Biomedical subjects

C Alberti

Publications and source records attributed to C Alberti.

At least 55 records · Page 3Linked to original sources

The influence of interstitial telomeric sequences on chromosome instability in human cells.

Although most telomere repeat sequences are found at the ends of chromosomes, some telomeric repeat sequences are also found at intrachromosomal locations in mammalian cells. Several studies have found that these interstitial telomeric repeat sequences can promote chromosome instability in rodent cells, either spontaneously or following ionizing radiation. In the present study we describe the extensive cytogenetic analysis of three different human cell lines with plasmids containing telomeric repeat sequences integrated at interstitial sites. In two of these cell lines, Q18 and P8SX, instability has been detected in the chromosome containing the integrated plasmid, involving breakage/fusion/bridge cycles or amplification of the plasmid DNA, respectively. However, the data suggest that the instability observed is characteristic of the general instability in these cell lines and that the telomeric repeat sequences themselves are not responsible. Consistent with this interpretation, the chromosome containing an integrated plasmid with 500 bp of telomeric repeat sequences is highly stable in the third cell line, SNG28, which has a relatively stable genome. The stability of the chromosome containing the integrated plasmid sequences in SNG28 makes this an excellent cell line to study the effect of ionizing radiation on the stability of interstitial telomeric sequences in human cells.

Carcinoma, Squamous Cell↗

A model to compute the medical cost of patients in intensive care.

OBJECTIVE: Our objective was to identify, among the information routinely collected on patients in intensive care units (ICUs), data that determine the total cost for a given patient. DESIGN: We developed a model that could help physicians in medical ICUs to estimate the cost of care for their patients when no cost data were available at the individual patient level. SETTING: A Medical ICU. PATIENTS AND PARTICIPANTS: The model was developed using a random sample of 73 patients admitted to the medical ICU in 1996 and 1997, validated by another random sample of 29 patients admitted during the same period. INTERVENTIONS: The actual medical variable cost per patient was computed from data on the total resources used (excluding personnel and fixed costs), collected from the patients' records plus pharmacy, laboratory and blood bank logs. The explanatory variables tested were: length of stay, nursing workload, severity of condition, and procedures recorded by a score [omega (omega)] including 3 components related to the frequency of procedure use. The model was constructed in a stepwise fashion, assuming a linear relation. Equations were tested on the basis of the residual mean square; criteria for inclusion and elimination of variables were the level of its partial regression coefficient and medical criteria. The model was validated by analysis of variance of the regression on a second population of 29 patients using the F-test. MAIN OUTCOME MEASURES AND RESULTS: The median length of stay was 7 days (range: 3 to 22 days). Mortality rate was 25%. Median medical variable cost was 805 Pounds (mean medical variable cost was 1738 Pounds, total cost was 6279 Pounds). The variables selected in the multiple regression model as relevant predictors of medical costs were: procedures recorded only once during the ICU stay irrespective of their reiteration (omega 1), procedures recorded every time they are performed (omega 2), procedures recorded daily in the ICU (omega 3) and the presence or absence of an invasive procedure (Kc). The final equation, calibrated with r2 of 0.826 and p > 0.0001, was: medical cost (Pounds) = 23 omega 1 + 53 omega 2 + 8 omega 3 + 2352Kc + 96. The validation with the other sample of 29 patients compared actual to predicted costs. Analysis of variance of the regression from the model was r2 = 0.596 (p > 0.05). CONCLUSIONS: Our standardised cost model is a possible approach to allow comparison of medical costs within and between ICUs.

Adult↗

Renovascular hypertension. Clinical and diagnostic clues.

Renovascular hypertension (RVH), although relatively rare, is the most frequent among the secondary forms of arterial hypertension; in addition interventional radiology has remarkably increased, because of its relative invasiveness, the possibilities of treating and in many cases curing RVH bypassing the traditional surgical approach. For these reasons in recent years a number of screening tests has been developed and added to renal angiography and to the measurement of plasma renin which, still now, represent the reference methods among the morphological and the functional tests respectively. These new and promising techniques include the magnetic resonance angiography, the spiral computed tomography, the renal scintigraphy and the ultrasound scanning of renal arteries with the associated measurement of velocimetric indices. In selected populations all these methods have been shown to possess an high specificity and sensitivity but if applied to a general population of hypertensive patients their positive predictive values are going to be necessarily low because of the low prevalence of the disease. Accordingly, it is mandatory for the physician, before sending patients to these investigations, to preselect those who, on the basis of a thorough clinical examination are more likely to harbour a renal artery stenosis.

Diagnosis, Differential↗

Effects of balloon angioplasty and stent implantation on intrarenal echo-Doppler velocimetric indices.

This study was aimed at examining whether four intrarenal echo-Doppler velocimetric indices (pulsatility and resistive indices, acceleration and acceleration time) can be useful for assessing the effects of renal artery dilation obtained with either angioplasty or stent implantation. Echo-Doppler studies were performed in 63 hypertensive patients with 68 renal artery stenoses (39 atherosclerotic and 29 fibromuscular) prior to and within five days after the dilation procedures (55 angioplasties, 13 stent implantations), which resulted in an average reduction of arterial narrowing from 79% to 20%. In 24 patients, the velocimetric indices were also examined in relationship to the venoarterial differences of plasma renin activity and of angiotensin II across the stenotic kidneys. We found that after dilation the values of the four indices had returned within the normal range in all but three arteries (one false negative for resistive index and two for acceleration time). However, decrements in acceleration time was the only factor to be significantly correlated with the reduction of arterial narrowing. Moreover, postdilation values of this index were, on average, slightly but significantly higher in arteries that at follow-up developed restenosis rather than in those that remained patent. For similar reductions in arterial narrowing the absolute changes of all indices were similar in atherosclerotic and fibromuscular stenotic arteries and, in a subset of the atheromatous arteries, were also similar after angioplasty and stent implantation. No relationship was found with the changes in the venoarterial differences of plasma renin activity and angiotensin II. It appears that these intrarenal velocimetric indices and, in particular, acceleration time reliably reflect the technical success of renal artery dilation. The acceleration time index may also be valuable for predicting the restenosis of the dilated vessel. None of the indices, however, mirrors the functional consequences of removal of renal artery stenosis as expressed through the changes in transrenal gradients of the components of the renin-angiotensin system.

Adolescent↗

Mechanism and pressor relevance of the short-term cardiovascular and renin excitatory actions of the selective A2A-adenosine receptor agonists.

Selective A2A adenosine receptor agonists are potent vasodilators that reduce blood pressure and induce marked increments in heart rate and plasma renin activity (PRA). To examine the mechanisms and pressor relevance of these cardiac and renin responses, we measured blood pressure and heart rate by telemetry and PRA in separate sets of spontaneously hypertensive rats (SHRs), which were given i.p. 2-hexynyl-5-methylcarboxamidoadenosine (2HE-NECA, 0.01 mg/kg) and 2-[4-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosin e (CGS 21680, 0.1 mg/kg) alone and after pretreatment with the beta 1-adrenoceptor blocking agent atenolol (100 mg/kg). The effects of 2HE-NECA (0.003 mg/kg) also were examined after pretreatment with the angiotensin-converting enzyme (ACE) inhibitor spirapril (3 mg/kg). Both A2A agonists induced marked reductions in blood pressure, associated with significant increments in heart rate and in PRA. Atenolol reduced blood pressure to the same extent as did the A2A agonists and markedly decreased heart rate and PRA. Pretreatment with atenolol entirely prevented the increase in heart rate and in PRA induced by the two A2A agonists but potentiated only slightly their antihypertensive effect. Spirapril alone reduced blood pressure and increased PRA and when given before 2HE-NECA potentiated its depressor and renin-stimulating effects by 44% and 69%, respectively. These results suggest that the increase in heart rate and in PRA induced by A2A agonists is the result of a reflex increase in sympathetic activity triggered by the decrease in blood pressure rather than of a direct stimulating effect on cardiac and renal A2A-adenosine receptors; the reactive activation of the renin-angiotensin system elicited by these compounds may contribute to blunting their antihypertensive effect.

Adenosine↗

[Uroangiographic contrast media, today. Elements of interest for the urologist].

Uroangiographic contrast media, as well as magnetic resonance or ultrasound contrast agents, are substances which are able to artificially enhance the contrast between different tissues, or between normal tissue and pathological areas. The design of ionic and nonionic, monomeric or dimeric, iodobenzene derivatives is outlined with attention given to historical developments and breakthroughs. Relationships between physicochemical properties (osmolality, viscosity, molecular structure, etc.) and pharmacological profile are described. Nonionic compounds display favourable physicochemical characteristics: high water solubility, low osmolality and viscosity and good systemic tolerability. Recent surveys on adverse reactions to uroangiographic iodinated contrast media have shown that the risk of severe reactions is about six times lower with nonionic than ionic X-ray contrast agents. The pathogenetic mechanisms of adverse reactions, generally classified as either anaphylactoid or osmotoxic and chemotoxic, are still not well understood. It has been proposed that leukotrienes, prostaglandins, kinins, etc., may be involved. Nitric oxide appears to play a crucial role in the final common pathway by which anaphylaxis-like reactions occur in response to contrast agent administration. The margin of safety (median lethal dose/diagnostic dose) for nonionic compounds is two- to three-fold greater than for ionic compounds. As a look at the future, an approach to molecules potentially useful as "blood pool X-ray contrast agents" is based on iodinated dendrimeric macromolecules, in which the core is triazacyclononane and branches are represented by trioodobenzene derivatives.

Contrast Media↗

The Logistic Organ Dysfunction system. A new way to assess organ dysfunction in the intensive care unit. ICU Scoring Group.

OBJECTIVE: To develop an objective method for assessing organ dysfunction among intensive care unit (ICU) patients on the first day of the ICU stay. DESIGN AND SETTING: Physiological variables defined dysfunction in 6 organ systems. Logistic regression techniques were used to determine severity levels and relative weights for the Logistic Organ Dysfunction (LOD) score and for conversion of the LOD score to a probability of mortality. PATIENTS: A total of 13 152 consecutive admission to 137 adult medical/surgical ICUs in 12 countries from the European/North American Study of Severity Systems. OUTCOME MEASURES: Patient vital status at hospital discharge. RESULTS: The LOD System identified from 1 to 3 levels of organ dysfunction for 6 organ systems: neurologic, cardiovascular, renal, pulmonary, hematologic, and hepatic. From 1 to 5 LOD points were assigned to the levels of severity, and the resulting LOD scores ranged from 0 to 22 points. Model calibration was very good in the developmental and validation samples (P=.21 and P=.50, respectively), as was model discrimination (area under the receiver operating characteristic curves of 0.843 and 0.850, respectively). CONCLUSION: The LOD System provides an objective tool for assessing severity levels for organ dysfunction in the ICU, a critical component in the conduct of clinical trials. Neurologic, cardiovascular, and renal dysfunction were the most severe organ dysfunctions, followed by pulmonary and hematologic dysfunction, with hepatic dysfunction the least severe. The LOD System takes into account both the relative severity among organ systems and the degree of severity within an organ system.

Adult↗

Superiority of acceleration and acceleration time over pulsatility and resistance indices as screening tests for renal artery stenosis.

OBJECTIVE: To compare the accuracy of four echo-Doppler-derived velocimetric indices (pulsatility and resistance indices, acceleration and acceleration time) in detecting renal artery stenosis in hypertensive patients. PATIENTS AND METHODS: In 73 hospitalized patients with moderate-to-severe hypertension, 18 of whom had normal renal arteries and 55 renal artery stenosis (50-95%) either atherosclerotic (30 cases, five bilateral) or fibromuscular dysplasia (25 cases, two bilateral), we measured the four velocimetric indices using the lateral abdominal approach and sampling Doppler waveforms distally to the stenosis. The diagnostic accuracy of each index was calculated using as cut-off limit the ideal threshold determined with the receiver-operating characteristic curves. RESULTS: On average all of the indices were altered significantly in arteries with stenosis of both aetiologies with respect to normal arteries, the alterations of pulsatility and resistance indices being, however, less pronounced than those of acceleration and acceleration time, particularly in atherosclerotic stenosis. With the cut-off limits of 0.93, 0.59 and 7.4 m/s2 and 60 ms, respectively, for pulsatility and resistance indices, acceleration and acceleration time, their diagnostic accuracies were 80, 73, 93 and 92%. In stenotic arteries, only the acceleration time was correlated with the degree of arterial narrowing, whereas, in normal arteries, only pulsatility and resistance indices were directly correlated with the age of patients. CONCLUSIONS: Acceleration and acceleration time are more accurate indices than pulsatility and resistance to screen for renal artery stenosis, probably because their alterations are less attenuated by the counterbalancing effects of age and of atherosclerosis.

Acceleration↗

Humoral effects of selective adenosine agonists in spontaneously hypertensive rats.

OBJECTIVE: We studied the dose-response effects of acute administration of the selective A1 adenosine receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA), the selective A2A agonists 2-hexynyl-5'-N-ethylcarboxamidoadenosine (2HE-NECA) and 2-[4-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680) and the non-selective agonist N-ethylcarboxamidoadenosine (NECA) on plasma renin activity, atrial natriuretic peptide, cyclic guanosine 3',5'-monophosphate (cGMP) and endothelin-1 in spontaneously hypertensive rats. METHODS: The drugs were administered intraperitoneally in four doses to conscious rats. Systolic blood pressure and heart rate were measured by the tail-cuff technique. Both humoral and hemodynamic parameters were determined 1 h after dosing in separate sets of animals. RESULTS: All the compounds induced a dose-dependent decrease in systolic blood pressure that was associated with different changes in heart rate. Heart rate was decreased by all doses of CCPA and by the higher doses of the non-selective compound (NECA) and increased by both A2A agonists. Plasma renin activity also changed in opposite directions, being decreased by CCPA but increased dose-dependently by 2HE-NECA and CGS 21680 and only moderately by NECA. Plasma atrial natriuretic peptide and cGMP levels increased dose-dependently after CCPA and NECA, but were unaffected by the A2A agonists. None of the compounds altered plasma endothelin-1 levels. CONCLUSIONS: These results indicate that the renin-suppressive effect of the A1 agonist, which is associated with a cardiodepressant action, may be attributed either to a direct inhibition of renin release or to the concomitant increments in plasma atrial natriuretic peptide and its second messenger, cGMP. In contrast, the renin-stimulating effect of the A2A agonists may result either from direct stimulation of renin secretion or from reflex sympathetic activation secondary to the fall in blood pressure.

Adenosine↗

Methylprednisolone and cyclophosphamide pulse therapy in crescentic glomerulonephritis: safety and effectiveness.

In a previous study, we found that aggressive immunosuppressive therapy with continuous high-dose oral steroid and cyclophosphamide combined with plasma exchanges for extracapillary crescentic glomerulonephritis gave controversial results since, although disease activity was controlled, iatrogenic complications had led to death in some aged patients. We then modified our therapeutic regimen, and we analyze here the evolution of 30 consecutive patients who were admitted for biopsy-proven crescentic glomerulonephritis between 1989 and 1991. The mean plasma creatinine level at admission was 393 +/- 59 mumol/L (range 70 to 1100), and 15 patients had crescent formation in more than 50% of glomeruli on initial renal biopsy. Ten patients did not receive any immunosuppressive treatment since they either had a normal renal function or they had terminal renal failure and no severe extrarenal manifestation. The 20 other patients received initial steroid pulses 500 mg x3 (n = 17), low oral steroid treatment (n = 20), cyclophosphamide pulses (n = 13), or oral cyclophosphamide (n = 3). In 4 cases plasma exchanges were also used. As a whole, 10 patients (33%) were discharged with a normal renal function, and 18 patients (60%) had chronic renal failure, 7 of them requiring dialysis or transplantation; only 2 patients died of pulmonary hemorrhage. No severe iatrogenic complication was observed. These results indicate that reduction in oral steroid dosage, cyclophosphamide pulse therapy rather than continuous oral treatment, and plasma exchanges do not induce overimmunosuppression and iatrogenic complication. It can be safe, well tolerated, and as effective as a more intensive immunosuppressive regimen for the treatment of crescentic extracapillary glomerulonephritis.

Actuarial Analysis↗

[Urothelial tumors and the extracellular matrix].

The network of both intra- and intercellular, either physical (bioconductive connectional system) and/or chemical signals, plays a significant role in the maintenance of tissue architecture and integrity of epithelial cell layers. The basement membrane is not only a static barrier but a dynamic regulator of the urothelium. Any change in the basement membrane can lead, by the extracellular matrix-cytoskeleton-nuclear matrix interaction, to altered gene regulation of the urothelial cells. Abnormal production and deposition or proteolytic degradation of the extracellular matrix components correlate with tumour stage and progression. In some experimental models, tissue inhibitors of metalloproteinases or anti-proteinase antibodies can abrogate the proteolytic activity of those matrix metalloproteinase enzymes (collagenase IV, cathepsin, stromelysin, etc.) which promote tumour invasion. Finally, the current researches investigating the use of biologic protein (e.g., TIMP-1 e-2; agents that affect angiogenesis and spread of neoplasias) are aimed at offer new therapeutic opportunities in oncology.

Basement Membrane↗

[Role of nitric oxide in the erectile mechanism].

Nitric oxide has been identified as an Endothelium-Derived Relaxing Factor (EDRF). Non adrenergic-non cholinergic nerves synthesise and release nitric oxide, thus modulating the arterial tone. Nitric oxide synthase exists either as a constitutive enzyme in many cell types and as an inducible form expressed under immunological stimulation. Nitric oxide is also involved in the non adrenergic-non cholinergic neurotransmission that leads to smooth muscle relaxation in the corpus cavernosum. Similarly nitric oxide induces reduction of cytosolic free Ca++ as a result of activation of the soluble form of guanylyl cyclase. VIP and nitric oxide may function as co-transmitters. Relaxation of the corpus cavernosum is blocked by methylene blue which inhibits cyclic GMP synthesis; so, high flow priapism refractory to medical and surgical treatments can be managed successfully by intracavernous methylene blue. Moreover it is suggested that enhanced alpha 1-adrenergic mediated constrictor tone and penile flaccidity in diabetic men may respond to exogenous generators of nitric oxide. We postulate that relaxation of the corpus cavernosum, started by nitric oxide in response to non adrenergic-non cholinergic neurotransmission, could be amplified and maintained by nitric oxide production as a result of platelet trapping in the corpus cavernosum during the first phase of the penile erection.

Amino Acid Oxidoreductases↗

[Prognosis of rapidly progressive glomerulonephritis: the influence of age].

The evolution and prognosis of extracapillary glomerulonephritis were compared in two cohorts of patients treated between 1981 and 1986 (n = 39) and between 1989 and 1991 (n = 30). In the first group, the classical immunosuppressive treatment (steroids and cyclophosphamide) was given daily and combined with plasma exchanges. In the second group, IV pulses of methylprednisolone and cyclophosphamide were administered, followed by daily low-dose steroid therapy. Plasma exchanges were performed only in cases of extrarenal disease, particularly pulmonary hemorrhage. Although the two groups are not strictly similar, it could be concluded that aggressive immunosuppression including plasma exchanges impairs the vital prognosis by inducing infectious and/or hemorrhagic complications, especially in the elderly. On the other hand, methylprednisolone and cyclophosphamide pulses appear to have effectively treated extracapillary glomerulonephritis and were well tolerated. Thus they could be administered to all patients with rapidly progressive glomerulonephritis, including aged patients.

Adolescent↗

Retroperitoneal fibrosis: some new acquisitions about pathogenesis and diagnostics.

Some newly proposed pathogenetic theories for retroperitoneal fibrosis refer to immune-related mechanisms; they are reviewed and discussed. In the field of imaging techniques, some MR paramagnetic contrast media, such as "ferrite" compounds and Gd-DTPA, and 67Ga-scintiscan, 111In-labelled leukocytes scan, 99mTc-labelled colloids contribute to answering the request to differentiate the still active cellulitis from an established fibrosis. 131I-MIGB scan identifies the carcinoid-related retroperitoneal fibrosis.

Humans↗