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Biomedical subjects

P Romano

Publications and source records attributed to P Romano.

At least 73 records · Page 4Linked to original sources

Changes in plasma warfarin levels and variations in steady-state prothrombin times.

OBJECTIVE: To determine the relative contribution of changes in the plasma warfarin level to variation in the serial steady-state prothrombin times. METHODS: This was a prospective observational cohort study performed at two outpatient anticoagulation clinics. Serial prothrombin times and paired plasma total warfarin levels were determined in a convenience sample of otherwise healthy patients who required long-term oral anticoagulation therapy with warfarin. RESULTS: Serial measurements were obtained from 129 patients, 60 of whom provided three or more serial samples. Analysis of covariance showed a highly significant (p = 0.0001) relationship between the anticoagulant effect and the logarithm of the warfarin concentration (R2 = 0.75), with 15.3% of the total variance attributable to the effect of warfarin and 31.1% attributable to individual variation in sensitivity to warfarin. In an analysis of the subjects who had three or more serial measurements, the mean weighted correlation coefficient for the relationship between the logarithm of the warfarin concentration and the anticoagulant response varied widely, from strongly negative to strongly positive, and as the range of observed prothrombin times increased, stronger positive correlation was observed. CONCLUSIONS: In this cohort, the plasma warfarin level was a strong predictor of observed changes in serial prothrombin time measurements. However, the correlation between clotting times and warfarin levels varied widely among subjects, particularly when the range of observed prothrombin times was moderate. This suggests that in these subjects, other factors, such as measurement error or pharmacodynamic changes, played a major role.

Adult↗

Interleukin-2-induced renal dysfunction in cancer patients is reversed by low-dose dopamine infusion.

Recombinant interleukin-2 (rIL-2) is widely used in patients with advanced cancer to enhance killer cell functions. However, the main drawback of rIL-2 therapy is the frequent development of oliguric acute renal failure (ARF), presumably due to a vascular leak syndrome. The aim of this study was to evaluate the effect of low-dose dopamine infusion on this form of ARF. Nine patients with metastatic renal cancer and previous unilateral nephrectomy were treated with a continuous intravenous infusion of rIL-2 (3 x 10(6) Cetus units/m2/d) for 5 days (study A). After 1 week, all the patients repeated the same cycle, but with the addition of a continuous intravenous infusion of dopamine (2 micrograms/min/kg body weight) that was started at the third day of treatment (study B). During study A, all patients showed a progressive (up to 34%) decrease of creatinine clearance. After rIL-2 withdrawal, these alterations persisted and were associated with a reduction in urinary output, sodium urinary excretion, and plasma protein. In study B, dopamine administration after renal function impairment (delta glomerular filtration rate = -44%) led to a prompt improvement of creatinine clearance. Creatinine clearance showed a further significant enhancement after the withdrawal of both drugs, reaching a value within the baseline range on the third day of follow-up. Similarly, the decline in urinary output and sodium excretion during rIL-2 was promptly counteracted by dopamine; in addition, after withdrawal of rIL-2 and dopamine, plasma protein levels were normalized. In conclusion, our data suggest that rIL-2-induced ARF in cancer patients is due to renal hypoperfusion mainly caused by a reduction in oncotic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Production of high levels of acetoin in Saccharomyces cerevisiae wine yeasts is a recessive trait.

A genetic study of acetoin production was performed on wild wine yeast strains of Saccharomyces cerevisiae producing different amounts of the compound. By using differences found in these strains as source of genetic variability, it was found that crosses between high and low acetoin producing strains yielded the low level in the hybrids, indicating the low production as a dominant trait. Tetrad analysis showed that high vs low acetoin production is segregated as a single gene.

Acetoin↗

Acetaldehyde production in Saccharomyces cerevisiae wine yeasts.

Eighty-six strains of Saccharomyces cerevisiae were investigated for their ability to produce acetaldehyde in synthetic medium and in grape must. Acetaldehyde production did not differ significantly between the two media, ranging from a few mg/l to about 60 mg/l, and was found to be a strain characteristic. The fermentation temperature of 30 degrees C considerably increased the acetaldehyde produced. This study allowed us to assign the strains to different phenotypes: low, medium and high acetaldehyde producers. The low and high phenotypes differed considerably also in the production of acetic acid, acetoin and higher alcohols and can be useful for studying acetaldehyde production in S. cerevisiae, both from the technological and genetic point of view.

Acetaldehyde↗

[Epidemiology and results of organ grafts].

Using the complete, multicentric Registry of organ transplantation in France, from 1970 to 1992, including 26,485 transplantations (kidney, heart, heart-lungs, lungs, liver), we studied four statistical parametres: 1. movement on the waiting list; 2. mean waiting time; 3. actuarial survival of the graft for the kidney, heart and liver; 4. number of recipients surviving with a functioning graft as of 31 December 1992. Patients awaiting a kidney transplant comprise a group that differs epidemiologically from the others on the basis of the length of the waiting list, entering and existing flux, and for the mortality rate of patients waiting for a graft. Similarly, the actuarial survival profile is different for the first year in kidney transplant recipients compared to the others.

France↗

Characterization of the KIN2 gene product in Saccharomyces cerevisiae and comparison between the kinase activities of p145KIN1 and p145KIN2.

We have isolated two yeast genes, KIN1 and KIN2, by their homology to the protein kinase family of viral oncogenes. Previous studies have identified the yeast KIN1 gene product (pp145KIN1) as a 145 kilodalton (kDa) phosphoprotein with serine/threonine-specific protein kinase activity. To identify and biochemically characterize the KIN2 gene product, antibodies were raised against a bacterial beta-galactosidase/KIN2 fusion polypeptide. In vivo, the KIN2 gene product is a 145 kDa phosphoprotein, pp145KIN2. In immune complexes, pp145KIN2 demonstrates serine/threonine protein kinase activity, transferring phosphate from [gamma-32P]ATP to either itself or the exogenously added substrates alpha-casein, acid-denatured enolase, or phosvitin. In vitro, kinase activity is dependent on either Mn2+ or Mg2+ ions. Both enzymes, pp145KIN1 and pp145KIN2, prefer ATP over GTP as their phosphoryl donor. Since a new class of yeast protein kinases has been identified which are serine/tyrosine-specific, we analysed a wide range of substrates to see if any could be phosphorylated by pp145KIN1 or pp145KIN2 on tyrosine residues. Both enzymes phosphorylate alpha-casein, acid-denatured enolase, and phosvitin on serine and threonine residues. Neither enzyme could phosphorylate tyrosine residues even though good substrates for tyrosine-specific kinases such as enolase, angiotensin II, and the synthetic polymer GLU80TYR20 were used. The biochemical analysis of KIN2 kinase activity shows remarkable similarity to that of its most closely related yeast kinase, KIN1. It remains to be seen if these two yeast protein kinases share any functional relationships or substrates in vivo.

Fungal Proteins↗

Genome renewal: a new phenomenon revealed from a genetic study of 43 strains of Saccharomyces cerevisiae derived from natural fermentation of grape musts.

We have analyzed by genetic means 43 strains of Saccharomyces that had been isolated from fermenting grape musts in Italy. Twenty eight of these strains were isolated from 28 cellars in the Region of Emilia Romagna. The other 15 strains came from 5 fermentations at four cellars near the city of Arpino, which is located south and east of Rome. We found that 20 of the 28 strains from Emilia Romagna were heterozygous at from one to seven loci. The balance were, within the limits of our detection, completely homozygous. All these strains appeared to be diploid and most were homozygous for the homothallism gene (HO/HO). Spore viability varied greatly between the different strains and showed an inverse relation with the degree of heterozygosity. Several of the strains, and in particular those from Arpino, yielded asci that came from genetically different cells. These different cells could be interpreted to have arisen from a heterozygote that had sporulated and, because of the HO gene, yielded homozygous diploid spore clones. We propose that natural wine yeast strains can undergo such changes and thereby change a multiple heterozygote into completely homozygous diploids, some of which may replace the original heterozygous diploid. We call this process 'genome renewal'.

Fermentation↗

Molecular Probe Data Base (MPDB).

This paper provides an update on the contents and structure, forms and mode of data distribution of the Molecular Probe Data Base (MPDB), a database that collects and provides on-line information on the sequence, target gene, applications and bibliographic references of synthetic oligonucleotides. The recent data extension and the new means of accessing the database are discussed.

Base Sequence↗

[Laser-assisted angioplasty in chronic obliterative arteriopathies of the lower limbs. The authors' personal experience].

The laser represents one of the most interesting new methods of vascular surgery. As for laser-assisted angioplasty, the major clinical experience has come with Nd: Yag and Argon lasers. The authors comment on the 1989-1992 series of cases consisting of 51 arteries recanalized with a Nd:Yag laser--the patients were 42 men and 9 women, their mean age being 56.6 years. Four iliac obliterations, 36 femoropopliteal and 11 popliteotibial obliterations were treated surgically, according to the single anatomical radiologic circumstances. The immediate results showed 41 recanalizations (80.4%) 3 perforations (5.9%), 6 dissections (11.8%) and 2 distal emboli (3.9%). The long-term results, with a follow-up period ranging 6 months to 4 years (average: 1.8 years), were investigated with seriated c.w. Doppler, Doppler US and digital venous angiography and showed, in 34 examined patients, 22 patencies (64.7%), 8 stenoses > 50% (23.5%) and 3 occlusions (11.8%). These findings prove the value of laser-assisted--both percutaneous and surgical--angioplasty in the treatment of arterial occlusions both alone and combined with surgery. The results, whose positivity comes also from an eclectic interaction with surgery, and mostly from a systematic enhancement of the laser channel with balloon angioplasty, could be markedly improved upon by means of more selective and effective equipment.

Adult↗

Molecular Probe Data Base: a database on synthetic oligonucleotides.

The Molecular Probe Data Base (MPDB) was designed to collect and make information on synthetic oligonucleotides available on-line. This paper briefly describes its purpose, contents and structure, forms and mode of data distribution. Particular emphasis is given to recent data extension and system enhancements that have been carried out in order to simplify access to MPDB for unskilled users.

Base Sequence↗

In situ lung perfusion with cisplatin. An experimental study.

BACKGROUND: This research work was planned to evaluate the soundness of in situ lung perfusion as a regional administration modality of chemotherapeutic agents. METHODS: Sixteen pigs were randomly divided into four groups and received cisplatin (2.5 mg/kg) through the pulmonary artery using one of the following techniques: stop-flow (Group 1); stop-flow/out-flow occlusion (Group 2); lung perfusion (Group 3); or lung perfusion with 5 mg/kg of infused drug (Group 4). Serial blood (carotid, pulmonary artery and vein) and tissue samples (lung and mediastinal node), were taken before, at completion of, and 5, 10, 15, 30, 60, 120, 180 and 240 minutes after cisplatin infusion for blood gas and platinum content measurement. Blood circulation was restored to the treated organ (for 60 minutes). The animals were killed, and specimens from lung, thyroid, esophagus, heart, liver, spleen, adrenal glands, kidney, bone marrow, stomach, ileum, colon, psoas muscle, and skin were obtained. Platinum concentrations in plasma, plasma ultrafiltrate (free platinum) urine, and tissues were determined by flameless atomic absorption spectroscopy. Lung damage was evaluated by light and electron microscopic examination. RESULTS: Greater systemic plasma, lower pulmonary plasma, and tissue platinum levels were detected when cisplatin was given using the stop-flow technique with respect to the other administration modalities. No significant difference in regional and systemic platinum exposure was found between Groups 2 and 3. However, lung perfusion resulted in higher mediastinal node and lower bone marrow platinum values. Morphologic alterations and impairment of gas exchanges in the treated lung were not dependent on the applied infusion technique. CONCLUSION: This study provides the pharmacokinetic rationale for the application of lung perfusion to patients with pulmonary metastases.

Animals↗