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Biomedical subjects

B Rocca

Publications and source records attributed to B Rocca.

At least 37 records · Page 2Linked to original sources

Serratia marcescens nosocomial outbreak due to contamination of hexetidine solution.

During a 10-week period, 16 patients in a neurosurgery intensive care unit were involved in an outbreak of Serratia marcescens. The epidemic strain was found in several flasks of 1:4 diluted hexetidine solution, an antiseptic used for patient mouth washing. Testing of the bactericidal activity of the diluted antiseptic revealed that all the epidemic strains were able to grow in the diluted antiseptic solution. Strains isolated from clinical samples and from the antiseptic solution were compared by random amplification of polymorphic DNA. Epidemiologic typing data implicated the diluted antiseptic solution as the single source of this S. marcescens outbreak.

Anti-Infective Agents, Local↗

Thrombin-thrombomodulin interaction: energetics and potential role of water as an allosteric effector.

The interaction of rabbit lung thrombomodulin (TM) and C-terminal hirudin 54-65 fragment (Hir54-65) with human alpha-thrombin were investigated by exploiting their competitive inhibition of thrombin-fibrinogen interaction. Measurements of Ki values for TM and Hir54-65 interactions with human alpha-thrombin performed over a temperature range spanning from 10 to 40 degrees C showed a constant enthalpy for both ligands. The enthalpic and entropic contributions to the free energy of binding, however, are different for TM and the hirudin peptide. The calculated values of delta H and delta S, in fact, were -47.3 +/- 2.51 kJ (-11.3 +/- 0.6 kcal)/mol and -42.7 +/- 7.9 J (-10.2 +/- 1.9 cal)/mol.K for the hirudin peptide, while being -22.9 +/- 2.09 kJ (-5.47 +/- 0.5 kcal)/mol and 102.50 +/- 6.69 J (24.5 +/- 1.6 cal)/mol.K respectively for TM binding. These findings indicate that the interaction between thrombin and Hir54-65 is largely driven by the enthalpic contribution, whereas the positive entropy change is the driving force for the formation of the thrombin-TM complex. In other experiments performed in the presence of various concentrations of either sorbitol or sucrose it could be demonstrated that the value of the equilibrium association constant for thrombin-TM interaction increases as a function of the osmotic pressure, while the thrombin-Hir54-65 interaction was not affected by the same conditions. Moreover, control experiments showed that no major conformational changes are produced on TM by osmotic pressures used in the present study. From these experiments it was calculated that roughly 35 water molecules are released into the bulk water upon TM binding. Such a phenomenon, which is likely to be responsible for the entropic change described above, indicates the relevance of hydration processes for the formation of the thrombin-TM adduct.

Allosteric Regulation↗

Increased thromboxane biosynthesis in essential thrombocythemia.

In order to investigate the in vivo thromboxane (TX) biosynthesis in essential thrombocythemia (ET), we measured the urinary excretion of the major enzymatic metabolites of TXB2, 11-dehydro-TXB2 and 2,3-dinor-TXB2 in 40 ET patients as well as in 26 gender- and age-matched controls. Urinary 11-dehydro-TXB2 was significantly higher (p < 0.001) in thrombocythemic patients (4,063 +/- 3,408 pg/mg creatinine; mean +/- SD) than in controls (504 +/- 267 pg/mg creatinine), with 34 patients (85%) having 11-dehydro-TXB2 > 2 SD above the control mean. Patients with platelet number < 1,000 x 10 (9)/1 (n = 25) had significantly higher (p < 0.05) 11-dehydro-TXB2 excretion than patients with higher platelet count (4,765 +/- 3,870 pg/mg creatinine, n = 25, versus 2,279 +/- 1,874 pg/mg creatinine, n = 15). Average excretion values of patients aging > 55 was significantly higher than in the younger group (4,784 +/- 3,948 pg/mg creatinine, n = 24, versus 2,405 +/- 1,885 pg/mg creatinine, n = 16, p < 0.05). Low-dose aspirin (50 mg/d for 7 days) largely suppressed 11-dehydro-TXB2 excretion in 7 thrombocythemic patients, thus suggesting that platelets were the main source of enhanced TXA2 biosynthesis. The platelet count-corrected 11-dehydro-TXB2 excretion was positively correlated with age (r = 0.325, n = 40, p < 0.05) and inversely correlated with platelet count (r = -0.381, n = 40, p < 0.05). In addition 11 out of 13 (85%) patients having increased count-corrected 11-dehydro-TXB2 excretion, belonged to the subgroup with age > 55 and platelet count < 1,000 x 10(9)/1. We conclude that in essential thrombocythemia: 1) enhanced 11-dehydro-TXB2 excretion largely reflects platelet activation in vivo; 2) age as well as platelet count appear to influence the determinants of platelet activation in this setting, and can help in assessing the thrombotic risk and therapeutic strategy in individual patients.

Adult↗

Effect of ketorolac, ketoprofen and nefopam on platelet function.

Ketorolac, ketoprofen and nefopam are often used in the treatment of postoperative pain. While nefopam is a non-narcotic, non-opioid central analgesic agent, ketorolac and ketoprofen are non-steroidal anti-inflammatory drugs, which, due to their prostaglandin-synthetase inhibiting activity, have antiplatelet effects. In this study we investigated the effect of ketorolac, ketoprofen and nefopam on platelet function by performing bleeding time and in vitro platelet aggregation in 30 healthy volunteers (10 for each treatment) before and 3 h after drug administration. Nefopam did not affect bleeding time and platelet aggregation, while ketorolac and ketoprofen significantly prolonged bleeding time without significantly inhibiting platelet aggregation in response to adenosine diphosphate. The prolongation of bleeding time observed after ketorolac and ketoprofen may have clinical relevance and suggests that nefopam could be more safely administered for the treatment of postoperative pain, especially in patients with haemostatic defects or after high bleeding risk surgery.

Bleeding Time↗

Effects of unfractionated and low molecular weight heparins on platelet thromboxane biosynthesis "in vivo".

Several "in vitro" and "in vivo" studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis "in vivo", as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionated heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 +/- 1388 vs 2092 +/- 777, p < 0.05; 2,3-dinor-TxB2: 2737 +/- 808 vs 1535 +/- 771 pg/mg creatinine, p < 0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation "in vivo" and suggest that the use of low molecular weight heparin may avoid this complication.

Adult↗

The linkage between binding of the C-terminal domain of hirudin and amidase activity in human alpha-thrombin.

A method derived from the analysis of viscosity effects on the hydrolysis of the amide substrates D-phenylalanylpipecolyl-arginine-p-nitroaniline, tosylglycylprolylarginine-p-nitroanaline and cyclohexylglycylalanylarginine-p-nitroalanine by human alpha-thrombin was developed to dissect the Michaelis-Menten parameters Km and kcat into the individual rate constants of the binding, acylation and deacylation reactions. This method was used to analyse the effect of the C-terminal hirudin (residues 54-65) [hir-(54-65)] domain on the binding and hydrolysis of the three substrates. The results showed that the C-terminal hir-(54-65) fragment affects only the acylation rate, which is increased approx. 1.2-fold for all the substrates. Analysis of the dependence of acylation rate constants on hirudin-fragment concentration, allowed the determination of the equilibrium binding constant of C-terminal hir-(54-65) (Kd approximately 0.7 microM). In addition this peptide was found to competitively inhibit thrombin-fibrinogen interaction with a Ki which is in excellent agreement with the equilibrium constant derived from viscosity experiments. These results demonstrate that binding of hir-(54-65) to the fibrinogen recognition site of thrombin does not affect the equilibrium binding of amide substrates, but induces only a small increase in the acylation rate of the hydrolysis reaction.

Amidohydrolases↗

Fechtner syndrome: report of a third family and literature review.

We observed macrothrombocytopenia with leucocyte inclusions in 10 out of 14 members of a four-generation family. Morphological features of leucocyte inclusions and the presence of Alport-related symptoms supported the diagnosis of Fechtner syndrome. Compared to the two previously reported Fechtner families, our kindred showed reduced expression of Alport manifestations. These, in members aged less than 50, were represented by clinically silent ocular abnormalities. Due to the frequent non-recognition of macrothrombocytopenia. Fechtner variants with low penetrance might be difficult to diagnose. In addition, Sebastian syndrome, recently distinguished from Fechtner disease in lacking Alport manifestations, might be one of these variants.

Adolescent↗

[Perioperative remote infections in neurosurgery. Role of antibiotic prophylaxis].

We report the results of a randomized, prospective study devised to assess the effectiveness of perioperative cefamandole prophylaxis on the remote infections rate in neurosurgery. Only two kinds of neurosurgical procedures were studied: shunt placement and craniotomy for brain tumour. In the treated patients cefamandole 1.5 g was given one hour before surgery, then repeated twice eight hourly. When the surgical procedure lasted more than three hours cefamandole 1.5 g was administered throughout the operation. No case of local infection was observed in either group, and the percentage of patients with remote infections was the same in both groups. Leucocytosis and temperature were measured during 15 days following the surgical procedure, and there were no differences between the treated and untreated groups in the evolution of these parameters. This study does not suggest that routine perioperative antibiotic prophylaxis is mandatory in neurosurgery.

Adolescent↗

Effect of fibrinogen concentration on the velocity of platelet aggregation.

The relationship between fibrinogen binding to its receptor and platelet aggregation has been investigated by comparing 125I-fibrinogen binding and aggregation velocities of gel-filtered platelets in the presence of adenosine diphosphate (ADP). Aggregometric responses at various fibrinogen concentrations are found to be bell-shaped and show a maximum at fibrinogen concentrations (Fmax) similar to the 125I-fibrinogen hemisaturating doses. At higher and lower fibrinogen concentrations, platelet aggregation velocities decrease in a parallel manner. Lowering ADP concentration increases Fmax, in agreement with the modulatory effect of ADP on fibrinogen binding to platelets. Variations of fibrinogen in the range of physiopathologic plasma concentrations affect platelet aggregation induced by any ADP dose. These results clarify the relationship between the fibrinogen binding process and aggregation and demonstrate that plasma fibrinogen concentration has a major influence on the velocity of platelet aggregation.

Adenosine Diphosphate↗

Comparison of four severity scores in patients with head trauma.

This study examines the performance of four severity scores in a group of 70 consecutive patients with head trauma, hospitalized in the same neurosurgical ICU. On day of admission to the ICU, data were collected from each patient to compute Acute Physiology Score (APS), Simplified Acute Physiology Score (SAPS), Glasgow Coma Scale (GCS), and Therapeutic Intervention Scoring System (TISS). These four scores were statistically correlated with the outcome of patients. Results also indicate that GCS was superior to any other score in predicting outcome of patients and allowed better specificity and sensitivity. Regarding the level of care needed by patients, TISS was superior to any other scoring system. The difficulty in estimating individual prognosis is discussed, since scoring systems are aimed at classifying groups of patients, not individuals. It is concluded that GCS is a simpler and less time consuming method in predicting outcome of patients with head trauma.

Adolescent↗

Familial autoimmune myasthenia gravis with different pathogenetic antibodies.

Two cases of familial myasthenia gravis are reported. One patient is a typical case of autoimmune myasthenia with positive anti acetylcholine receptor antibodies, while in the second patient the impairment of neuromuscular transmission is likely to be due to antibodies directed against determinants other than the acetylcholine receptors.

Adult↗

[Lack of prognostic value of the determination of 3 serum proteins during the acute phase of brain injury].

In has been suggested that monitoring of blood levels of serum proteins could be of value in order to assess the prognosis of trauma patients. A study was set up to assess the value of albuminaemia, prealbuminaemia, transferrin and ceruleoplasmin levels in intensive care unit patients admitted after multiple trauma including head injury. This study involved 43 patients (31 men and 12 women), with a mean age of 26 years (range: 15 and 71 years). Two patients had extradural haematoma. The other patients had brain contusion associated with extradural haematoma (5 cases), subdural haematoma (1 case) and open brain wound (1 case). All these patients were sedated with penthiobarbital, paralysed with pancuronium bromide and mechanically ventilated. Serum protein levels were measured on the first and eighth days of the stay in the intensive care unit. In these patients that survived, there was a significant decrease in albuminaemia and transferrin levels, no change in prealbuminaemia and a significant increase in ceruleoplasmin levels. Ten patients died during the study. They presented a greater decrease in albuminaemia and prealbuminaemia as compared with the survivors. There was no difference in the evolution of ceruleoplasmin and transferrin levels between the two groups. Thus, whilst the difference between survivors and non-survivors was significant for the group, for the individual patient the difference was too small to be of any prognostic value.

Acute-Phase Proteins↗