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Biomedical subjects

A Ferroni

Publications and source records attributed to A Ferroni.

At least 37 records · Page 2Linked to original sources

Molecular epidemiology of Streptococcus pyogenes in an area where acute pharyngotonsillitis is endemic.

During an open clinical trial in an area where streptococcal infections are hyperendemic, we studied the genetic polymorphism of Streptococcus pyogenes isolates collected from patients and from healthy carriers living in close contact with them. The clonal diversity of isolates was analyzed by pulsed-field gel electrophoresis with three restriction enzymes (SmaI, ApaI, and SacII). The pharynx of each patient and healthy carrier was colonized by a single clone, suggesting the clonal nature of streptococcal colonization in individuals. Among 52 isolates obtained from patients with acute pharyngotonsillitis, we found 14 genetically unrelated clones, showing the genetic diversity of S. pyogenes. However, two clones belonging to the M1 and M12 serotypes represented about 70% of isolates in carriers and patients. Pharyngeal colonization in cured patients was monitored for 3 to 4 months. After the initial elimination of S. pyogenes following antibiotic therapy, the rate of recolonization was high by day 30 (about 20%) and was also at that level between days 90 and 120; this was similar to the carriage rate in family contacts. Thus, cured patients can be recontaminated by unrelated clones, suggesting that colonization of healthy carriers might be a potential source of spread and redistribution of S. pyogenes isolates.

Acute Disease↗

Functional role of low-voltage-activated dihydropyridine-sensitive Ca channels during the action potential in adult rat sensory neurones.

Neuronal cell firing is crucial to nerve-nerve communication. The ability to produce consecutive action potentials is related to the activation of inward currents after each upstroke. If fast Na current is indeed responsible for the overshoot, it is still unclear which current drives membrane voltage to the Na threshold. In this study we present evidence that in adult rat sensory neurones a dihydropyridine-sensitive Ca channel exists in addition to the well characterized L-type, or high-threshold Ca channel. During stimulated action potential trains, L-type Ca channels open during the excitation wave, whereas activity of the other dihydropyridine-sensitive Ca channel was observed primarily between action potentials. This second Ca pathway shows remarkably long openings at negative potentials after a series of positive prepulses. The nerve action potential and the repetitive firing work as a physiological Ca channel facilitation mechanism. Therefore, we suggest that this novel Ca conductance provides inward current, between two consecutive action potentials, able to modulate the frequency of neuronal bursts.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Cytoskeletal control of rectification and expression of four substates in cardiac inward rectifier K+ channels.

Cardiac inward rectifiers may have a three-barrel channel structure, based on evidence for three substates in single-channel recordings. However, some reports indicate four substates, a feature more compatible with the four-subunit structure for which there is evidence in cloned voltage-activated K+ channels. Here we show that although the fourth is easily missed, inward rectifier channels have four substates whose expression is controlled by intracellular Ca(2+) ions. Fourth substate openings also appear after rectification loss in intracellular divalent caution-free solution. We find that this process is accelerated by cytochalasin, a microfilament disrupter. Cytochalasin also abolishes Ca(2+), but not Mg(2+),-induced rectification by restoring fourth substate openings. Thus, cytoskeletal elements control Ca(2+)-dependent substate expression and rectification in native inwardly rectifying K+ channels.

Animals↗

Clonal distribution of penicillin-resistant Streptococcus pneumoniae 23F in France.

We studied the clonality of clinical isolates of Streptococcus pneumoniae 23F, the serotype most often associated with penicillin resistance in France. Clinical isolates obtained between November 1992 and April 1993 from nasopharyngeal samples from children with acute otitis media from different regions of the country were analyzed. The genetic polymorphism of penicillin-susceptible and -resistant 23F isolates (MIC, 2 mg/liter) was studied by pulsed-field gel electrophoresis. The resistant isolates were closely related, whereas the susceptible isolates were genetically heterogeneous. PCR amplification and restriction of the genes encoding penicillin-binding proteins (PBPs) 1A, 2B, and 2X also showed that the 24 resistant isolates had similar patterns which were very different from those of the susceptible isolates. All resistant isolates gave the same PBP pattern, with low affinities of PBPs for penicillin. Our results indicate that, in contrast to penicillin-susceptible 23F isolates, the penicillin-resistant 23F isolates have a single clonal origin, suggesting the rapid clonal spread of a resistant epidemic strain throughout the country.

Bacterial Proteins↗

Chronic septic arthritis and osteomyelitis in a prosthetic knee joint due to Clostridium difficile.

A case of chronic septic arthritis and osteomyelitis in a prosthetic knee joint due to Clostridium difficile is reported. A knee prosthesis was installed in a 16-year-old boy for surgical treatment of an osteosarcoma of the femur. Later, the patient suffered a traumatic closed fracture of his patella, and a sterile fluid was aspirated. One month later, the joint displayed inflammation. Culture of the articular fluid yielded a nontoxigenic Clostridium difficile strain. Despite several attempts using conservative medical treatment with penicillins and ornidazole, Clostridium difficile strains with the same antibiotic susceptibility pattern were repeatedly isolated from the joint over an eight-month period. The foreign material was then ablated, and finally, the patient's leg was amputated one year after Clostridium difficile was first isolated. The possible sources of contamination in our case and other reported cases of extraintestinal infection due to Clostridium difficile are discussed.

Adolescent↗

So-called "petit mal status": epileptic syndrome or seizure type?

In 1945, Lennox was the first to describe the epileptic states mainly expressed by various degrees of consciousness disturbance, which have their onset in children who present epileptic absences correlated with ictal EEG patterns of spike-wave complex discharges at about 3 Hz. As the clinical picture seemed to be similar to an uninterrupted series of absences, this led to the definition "Petit Mal Status" (PMS). Many authors have subsequently reported that PMS can occur in epileptic subjects who have never presented absences (and even in subjects without a previous history of epilepsy) and that the related EEG pictures were characterised by paroxysmal generalized activity of various morphology, but hardly ever consisted of the continuous rhythmic spike-wave or polyspike-wave complexes at 3 Hz found in petit mal absences. Finally, in reporting the onset and recurrence of this condition typically in adults and the elderly, some authors have proposed the existence of a particular form of PMS (dependent on different types of pathologic factors and characterising a specific syndrome of this age) that is different from that of the "real PMS" typical of childhood and related to petit mal absences. This paper describes fifteen patients in whom the onset of the condition occurred at different ages, and who seem to exemplify the various possible clinical expressions of PMS, with the aim of making a contribution towards the better nosographic definition of this epileptic condition. On the basis of our study, we sustain that the so-called PMS is a seizure type of Idiopathic Generalized Epilepsy which may appear at nearly all ages, and may occur in isolation or in association with other epileptic manifestations, but cannot itself be considered as characterising one or more age-dependent syndromes.

Adolescent↗

Inactivation of single Ca2+ channels in rat sensory neurons by extracellular Ca2+.

1. Single Ca2+ channels conducting 20 mM Ba2+ from adult rat dorsal root ganglion cells were characterized using the two-electrode patch-clamp technique configuration. 2. Channels demonstrating specific characteristics of conductance, voltage dependence and dihydropyridine sensitivity were classified as high-threshold or L-type Ca2+ channels. 3. Mean single-channel current in 20 mM Ba2+ did not show inactivation, but inactivation occurred when using Ca2+ as a permeating ion. 4. Stimulus protocols were delivered alternately in the cell-attached and whole-cell electrode, while recording single-channel activity and total Ca2+ current simultaneously. 5. A mean single-channel Ba2+ current from a stimulated patch did not show inactivation. However, stimulation of a physiological whole-cell Ca2+ current induced a marked inactivation of mean single-channel Ba2+ current. 6. Complete Ca2+ current block by the addition of 200 microM Cd2+ in the external solution removed single-channel inactivation in patches stimulated through a whole-cell electrode.

Animals↗

Muscarinic regulation of Ca2+ currents in rat sensory neurons: channel and receptor types, dose-response relationships and cross-talk pathways.

We studied, in rat sensory neurons, the modulation of high voltage-activated Ca2+ currents (ICa) mediated by the pertussis toxin-sensitive activation of muscarinic receptors, which were found to be of subtypes M2 or M4. Muscarine reversibly blocked somatic Ca2+ spikes but strong predepolarizations only partially relieved the inhibited Ca2+ current. On the other hand, the putative coupling messenger could not rapidly diffuse towards channels whose activity was recorded from a macro-patch. The perforated patch technique virtually prevented the response rundown present during whole-cell experiments. Both omega-conotoxin GVIA (omega-CgTx)-sensitive channels and omega-CgTx- and dihydropyridine-resistant channels are coupled to the muscarinic receptor, but not the L-channel. When measured in the same neuron, dose-response relationships for the first and subsequent agonist applications differed; maximal inhibition, the reciprocal of half-maximal concentration and the Hill coefficient were always highest in the first trial. Muscarine and oxotremorine exhibited monotone dose-response curves, but oxotremorine-M showed non-linear relationships which became monotonic when cells were intracellularly perfused with inhibitors of protein kinase A (PKA) and C (PKC), suggesting that either PKA or receptor-induced PKC could phosphorylate and thus inactive G-proteins or other unknown proteins involved in inhibitory muscarinic actions on ICa. In summary, these data provide a preliminary pharmacological characterization of the muscarinic inhibition of the Ca2+ channels in sensory neurons, with implications about agonist specificity and the interplay between signalling pathways.

Action Potentials↗

Acyclovir in preventing cytomegalovirus infection in kidney transplant recipients: a case-controlled study.

High dose oral acyclovir has been reported to be effective in preventing both cytomegalovirus (CMV) infection and disease in renal transplant recipients. We conducted a case-controlled study in which 42 cadaveric kidney transplant recipients were prophylactically treated with high dose oral acyclovir for 3 months and compared to historical controls matched for donor/recipient CMV serological status, age, sex, and immunosuppressive therapy. Before transplantation, study group patients received acyclovir intravenously (500 mg/m2 over 1 hour) which was subsequently given orally (basal dose--800 mg four times daily) from day 2 post-transplantation according to renal function. All patients received 14-day induction immunosuppressive therapy with either a polyclonal or a monoclonal antibody together with low dose steroids and azathioprine, cyclosporin being introduced at day 10 post-transplantation. Blood viral cultures as well as CMV antibody titers were performed in study group and control patients in the same laboratory, before transplantation, weekly until 3 months and then monthly until 6 months. CMV infection was defined as a positive blood or bronchoalveolar lavage viral culture or presence of CMV IgM or CMV IgG in a previously seronegative patient. Diagnosis of CMV disease also required the presence of at least one concomitant febrile illness, with or without other clinical symptoms, not attributable to another pathogen. All patients were followed for 3 months. Incidence of both CMV infection and disease was compared in the two groups using the log-rank test. With regard to CMV infection, we found significantly less CMV infection in CMV seropositive patients (regardless of donor CMV serological status) in the study group compared to historical controls (P = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Acyclovir↗

Randomized study of two doses of didanosine in children infected with human immunodeficiency virus.

2'3'-Dideoxyinosine (didanosine) is a nucleoside analog active in vitro against human immunodeficiency virus. Few data are available regarding its use for the treatment of children. In a single-center, randomized, open-label trial, we compared two dosages of didanosine (120 vs 270 mg/m2 per day) for at least 6 months in 34 children infected with human immunodeficiency virus who had become resistant to or were intolerant of zidovudine. Serum levels of didanosine 1 hour after administration were significantly different in the two groups and remained stable with time. There was a significant reduction in human immunodeficiency virus-p24 antigenemia and quantitative cellular viremia with time but no difference between the two groups. The intensity of the biologic response, however, was significantly higher in the patients who had more than 50 CD4+ cells 10(6)/L at inclusion. No pancreatic or neurologic toxic effects were observed. In five children, liver function abnormalities developed that are unusual in this setting, and the death of one child from unexplained hepatocellular failure suggests that didanosine may be hepatotoxic. Three of these five children had preexisting liver disease. Although no definite conclusion can be made as to the optimal dose, there were no major differences between the two administration schedules in terms of biologic effects and tolerability.

Adolescent↗

The use of viral culture and p24 antigen testing to diagnose human immunodeficiency virus infection in neonates. The HIV Infection in Newborns French Collaborative Study Group.

BACKGROUND: Early diagnosis of human immunodeficiency virus (HIV) infection in infants born to infected mothers is important for the infants' medical care, but the presence of maternal antibodies makes serologic tests uninformative. METHODS: In a cohort study of 181 infants born to HIV-infected mothers, we assessed the diagnostic value of HIV viral culture and testing for the presence of p24 antigen. The infants were tested at birth, again during the first 3 months, then followed and tested at the age of at least 18 months. RESULTS: Of the 181 infants, 3 died of HIV infection and 37 were seropositive after the age of 18 months. Viral cultures at birth were positive in 19 of the 40 infected infants and in none of the uninfected infants, yielding a sensitivity of 48 percent (95 percent confidence interval, 32 to 63 percent) and a specificity of 100 percent (95 percent confidence interval, 97 to 100 percent). By the age of three months, 30 of the 40 infants (75 percent) had positive cultures; again, there were no false positive results among the infants who were tested a second time, of the 141 who remained uninfected. The sensitivity of testing for p24 antigen at birth was only 18 percent, with a specificity of 100 percent. The presence of p24 antigen at birth was associated with the development of early and severe HIV-related disease (P less than 0.04). CONCLUSIONS: Viral culture at birth can correctly identify about half of newborns with HIV infection. The fact that this usually sensitive technique fails to identify about half the ultimately infected neonates suggests that vertical transmission of HIV may occur late in pregnancy or during delivery.

False Negative Reactions↗

Effect of firing rate on the calcium permeability in adult neurons during spontaneous action potentials.

Calcium channels in neurons mediate a wide variety of essential functions. In addition to contributing to action potential shape, they furnish a substrate that acts as an intracellular second messenger. This study shows that the shape of the neuronal action potential has characteristics that promote long openings of L-type (high threshold) calcium channels. We also present evidence that a change in the firing rate of isolated neurons modulates gating of single calcium channels. This mechanism could be important in modulating neuron excitability and providing a rise in intracellular Ca, when needed.

Action Potentials↗

[Supraventricular tachyarrhythmias during acute myocardial infarction: short- and mid-term clinical significance, therapy and prevention of relapse].

Clinical significance, short and long-term prognostic value, and treatment of supraventricular tachyarrhythmias were evaluated in 208 patients with definite acute myocardial infarction (AMI). No patient received thrombolytic therapy. In Coronary Care Unit supraventricular tachyarrhythmias were detected by continuous electrocardiographic monitoring in 30 (14%) patients: 18 had atrial fibrillation, 1 atrial flutter, 9 paroxysmal atrial tachycardia and 2 non-paroxysmal junctional tachycardia. These episodes began within the first 48 hours of AMI in 93% of patients, and generally they were preceded by frequent or repetitive atrial premature beats. Supraventricular tachyarrhythmias were significantly associated with older age, higher incidence of overt left ventricular dysfunction (both p less than 0.05) and higher Peel Index (p less than 0.02). They caused severe hemodynamic consequences in 20% of patients. In 8 patients they were selflimiting, in 20 they were suppressed by means of medical therapy and in one by DC countershock. During hospitalization supraventricular tachyarrhythmias recurred in one patient; moreover, in this period cardiac death occurred in 26% of patients with supraventricular tachyarrhythmias and in 13% of the remaining (p: ns). Multivariate analysis showed that supraventricular tachyarrhythmias are not important factors in identifying patients at risk of cardiac death. At hospital discharge, patients with supraventricular tachyarrhythmias showed significantly higher values of left ventricular end-diastolic and end-systolic dimensions (both less than 0.05), and a greater use of digitalis-diuretics and/or vasodilators (p less than 0.03). By contrast, in patients with and without supraventricular tachyarrhythmias no significant difference was present with regard to the frequency of New York Heart Association functional classes III-IV for congestive heart failure, frequency of significant tachyarrhythmic events during 24-hour continuous electrocardiographic recording, X-ray cardiac size and left ventricular ejection fraction at rest. In the 2 years following AMI, survival curves showed no significant difference in the risk of cardiac death among patients with or without supraventricular tachyarrhythmias; in particular, in the first group only 2 patients had severe hemodynamic events and no patient showed recurrences of tachyarrhythmia. Our findings suggest that although supraventricular tachyarrhythmias complicating AMI frequently occur in patients with severe cardiac disease they are not related to a higher risk of cardiac death either during in-hospital period or in the 2 years following AMI; medical therapy is effective and safe to suppress these arrhythmias; a systematic use of specific antiarrhythmic drugs to prevent their recurrences is not necessary.

Adult↗

Frequency, characteristics and significance of supraventricular tachyarrhythmias detected by 24-hour electrocardiographic recording in the late hospital phase of acute myocardial infarction.

The incidence, characteristics and clinical significance of supraventricular tachyarrhythmias occurring in the late hospital phase of acute myocardial infarction (AMI) were assessed in 209 consecutive patients. Arrhythmias were quantified by 24-hour electrocardiographic recording 16 +/- 3 days after AMI, and were classified according to the degree of complexity in 5 classes. Class 0 = less than 5 premature beats/hr; class 1 = between 5 and 100/hr; class 2 = greater than 100/hr or repetitive premature beats; class 3 = atrial-junctional tachycardia; class 4 = atrial flutter-fibrillation. Supraventricular tachyarrhythmias classes 1 to 2 always occurred in the absence of symptoms in 86 patients (41%); supraventricular tachyarrhythmias classes 3 to 4 (paroxysmal, self-limiting, brief) occurred in 27 patients (13%), symptomatically in 6. The presence of supraventricular tachyarrhythmias classes 2 to 3 was related to age over 55 years and complex ventricular tachyarrhythmias (greater than 20 premature beats/hr, ventricular tachycardia) (both p less than 0.05). Increasing complexity of supraventricular tachyarrhythmias was significantly associated with presence and entity of cardiac enlargement and left ventricular dysfunction (both p less than 0.01). Patients with class 4 showed the most severe cardiac deterioration. During the 2 years after AMI, patients with classes 2, 3 and 4 had a higher incidence of acute pulmonary edema, New York Heart Association functional classes III to IV for congestive heart failure (both p less than 0.005) and a greater need of digitalis and diuretics (p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sodium current block caused by group IIb cations in calf Purkinje fibres and in guinea-pig ventricular myocytes.

The action of group IIb cations [Cadmium (Cd2+), Zinc (Zn2+), Mercury (Hg2+)] on the cardiac fast sodium current (INa) was investigated in calf Purkinje fibres and in ventricular cells isolated from guinea-pig hearts. In calf Purkinje fibres, INa was depressed by submillimolar concentrations of Zn2+ and Hg2+. With both cations, the current reduction occurred at all voltages in the range of current activation and the voltage dependence of peak current was unchanged. The degree of peak current inhibition depended on the cation concentration but not on voltage. The position of the inactivation curve on the voltage axis was unaltered at cation concentrations giving substantial current inhibition, and moved to the right only with concentration exceeding 1-1.5 mM. These effects can be interpreted as due to INa channel blockade. The action of Zn2+ and Hg2+ was similar to that described earlier of Cd2+ on Purkinje fibres (DiFrancesco et al. 1985b). INa was also inhibited by group IIb cations in isolated guinea-pig ventricular cells. Depression of INa by Cd2+, Zn2+ and Hg2+ was essentially voltage-independent, in agreement with its being caused by channel block. The dependence of INa block by Cd2+ upon external Na concentration [Na+0] was investigated in ventricular myocytes. The fraction of INa block by 0.1 mM CdCl2 was 0.50 at 140 mM, 0.81 at 70 mM and 0.83 at 35 mM [Na+]0. A similar increase of block efficiency at low [Na+0] was observed with 0.05 mM CdCl2. In both the Purkinje fibre and the ventricular cell, the order of potency of INa block by group IIb cations was Hg2+ greater than Zn2+ greater than Cd2+. Manganese (Mn2+, 2-5 mM), an ion of group VIIa, also depressed the INa in Purkinje fibres and ventricular myocytes. This effect was however due mainly to a positive shift on the voltage dependence of current kinetics rather than to a reduction of the conductance of the channel (GNa), and can be accounted for by an ion-screening action of Mn2+ on the external membrane surface. The block by group IIb cations is a typical property of cardiac Na+ channels and characterizes the cardiac as opposed to other types of Na+ channel.

Animals↗

Two high voltage-activated calcium currents are present in isolation in adult rat spinal neurons.

In neurons enzymatically isolated from adult rat dorsal root ganglia and used during the following 24 hours, the Ca2+ currents were investigated with the whole-cell patch-clamp technique. In contrast to the neonatal neurons, the salient feature of these adult neurons is the well separated (in the voltage-range) activation and inactivation properties of each recorded current. The low-threshold T-, the high-threshold inactivating N-, and the long-lasting L-currents have a threshold for activation at -60, -45 and -10 mV, and a 50% inactivation at -75, -45 and -5 mV respectively. The N and L currents were poorly affected by 100 microM Ni, a known blocker of T channels and completely blocked by 100 microM Cd2+. Frequently we could find neurons with only one type of current present. We conclude that adult sensory neurons are a better preparation for studying, in isolation, the physiological relevance of the three types of Ca2+ channels.

Aging↗