Biomedical subjects
Publications and source records attributed to G Ferrari.
Few data are reported on imaging in the Kearns-Sayre syndrome (KSS). We present the MRI findings in a case of KSS confirmed by mitochondrial DNA molecular analysis. MRI may prove useful in detection and delineation of this disease.
We describe a patient with defective tissue plasminogen activator (t-PA) release who developed internal cerebral vein thrombosis. She recovered completely and, as shown by MRI, favourable outcome was probably related to vascular recanalisation. Other members of the pedigree had a similar fibrinolytic deficiency without clinical manifestations. The use of oral contraceptives may have contributed to the patient's hypercoagulable state.
Active or passive immunisation with vaccines or sera can cause lesions of immunomediated pathogenesis involving both the central (CNS) and the peripheral nervous system (PNS). Although very rare, the neurological complications described during antitetanus vaccinations almost exclusively affect the PNS, those affecting the CNS being even more rare. The authors report a case of transverse myelitis with a radicular component, which arose acutely following the administration of tetanus toxoid and had a partially favourable course.
OBJECTIVE: To study the efficacy of the Dornier MPL 9000 lithotripter with a real time ultrasound transducer in the localization and treatment of upper and prevesical ureteric stones. PATIENTS AND METHODS: Two-hundred and eighty-five patients with pre-vesical ureteric stones and 247 patients with upper ureteric stones underwent extracorporeal shock wave lithotripsy (ESWL) using ultrasound targeting, under no regional or general anaesthesia. RESULTS: At follow-up after 3 months 97% of patients with pre-vesical stones and 96% with upper ureteric stones were stone free. Ninety-nine patients were treated more than once. The average number of sessions of ESWL for all patients was 1.19 (1.17 for patients with prevesical stones and 1.22 for those with upper ureteric stones). Ureteric stenting was employed in 6% of cases. The infrequent use of ureteric stenting did not reduce ESWL efficacy, nor increase either the complication or the retreatment rates. In many cases upper urinary tract dilatation was provoked by administering intravenous fluid and a diuretic. CONCLUSION: In situ echoguided ESWL is a simple, safe and effective technique for treating ureteric stones which can be detected on ultrasound.
The incidence of fast atrial tachycardias with regular ventricular rhythm was assessed in a population of 243 patients with recent onset (< 72 hours) atrial fibrillation (AF), without heart failure, randomly treated with single loading oral dose of propafenone (600 mg), flecainide (300 mg), digoxin (1 mg), or placebo for acute conversion to sinus rhythm (SR). Fast atrial arrhythmias developed in 14 (6%) patients: 6/92 treated with propafenone, 3/34 treated with flecainide, 1/25 treated with digoxin, and 4/92 who received placebo (P = NS). Heart rate > 175 beats/min with 1:1 AV conduction ensued in 4 cases: 2 treated with flecainide and 2 treated with placebo; in the other cases 2:1 AV conduction was observed. Widening of QRS during regular tachycardia was observed in 4 patients; 3 who received propafenone and 1 who received flecainide. Conversion to SR within 4 hours was achieved in 55/92 (60%) patients treated with propafenone, 20/34 (59%) patients treated with flecainide, 7/25 (28%) patients treated with digoxin, and 19/92 (20%) treated with placebo (P < 0.001 propafenone vs placebo and flecainide vs placebo; P < 0.05 propafenone vs digoxin and flecainide vs digoxin). Periods of regular tachycardia are expected in recent onset AF and may not necessarily represent a proarrhythmic effect of Class 1C drugs, rather than mark the transition from AF to SR. Class 1C agents are probably responsible for widening of the QRS complex seen during these tachycardias. Propafenone and flecainide appear equally effective in converting recent onset AF.
In order to assess the combined and separate effects of pancreas and kidney transplant on whole-body protein metabolism, 9 insulin-dependent diabetic-uremic patients (IDDUP), 14 patients after combined kidney-pancreas transplantation (KP-Tx), and 6 insulin-dependent diabetic patients with isolated kidney transplant (K-Tx), were studied in the basal postabsorptive state and during euglycemic hyperinsulinemia (study 1). [1-14C]Leucine infusion and indirect calorimetry were utilized to assess leucine metabolism. The subjects were studied again with a combined infusion of insulin and amino acids, given to mimic postprandial amino acid levels (study 2). In the basal state, IDDUP demonstrated with respect to normal subjects (CON): (a) higher free-insulin concentration (17.8 +/- 2.8 vs. 6.8 +/- 1.1 microU/ml, P < 0.01) (107 +/- 17 vs. 41 +/- 7 pM); (b) reduced plasma leucine (92 +/- 9 vs. 124 +/- 2 microM, P < 0.05), branched chain amino acids (BCAA) (297 +/- 34 vs. 416 +/- 10 microM, P < 0.05), endogenous leucine flux (ELF) (28.7 +/- 0.8 vs. 39.5 +/- 0.7 mumol.m-2.min-1, P < 0.01) and nonoxidative leucine disposal (NOLD) (20.7 +/- 0.2 vs. 32.0 +/- 0.7 mumol.m-2. min-1, P < 0.01); (c) similar leucine oxidation (LO) (8.0 +/- 0.1 vs. 7.5 +/- 0.1 mumol.m-2.min-1; P = NS). Both KP-Tx and K-Tx patients showed a complete normalization of plasma leucine (116 +/- 5 and 107 +/- 9 microM), ELF (38.1 +/- 0.1 and 38.5 +/- 0.9 mumol.m-2.min-1), and NOLD (28.3 +/- 0.6 and 31.0 +/- 1.3 mumol.m-2.min-1) (P = NS vs, CON). During hyperinsulinemia (study 1), IDDUP showed a defective decrease of leucine (42% vs. 53%; P < 0.05), BCAA (38% vs. 47%, P < 0.05), ELF (28% vs. 33%, P < 0.05), and LO (0% vs. 32%, P < 0.05) with respect to CON. Isolated kidney transplant reverted the defective inhibition of ELF (34%, P = NS vs. CON) of IDDUP, but not the inhibition of LO (18%, P < 0.05 vs. CON) by insulin. Combined kidney and pancreas transplanation normalized all kinetic parameters of insulin-mediated protein turnover. During combined hyperinsulinemia and hyperaminoacidemia (study 2), IDDUP showed a defective stimulation of NOLD (27.9 +/- 0.7 vs. 36.1 +/- 0.8 mumol.m-2.min-1, P < 0.01 compared to CON), which was normalized by transplantation (44.3 +/- 0.8 mumol.m-2.min-1).
The binding of riboflavin to rat small intestinal brush border membrane at equilibrium was formerly shown to have a saturable, specific component, prevailing at the intraluminal physiological concentrations of the vitamin. In this study, the specificity of riboflavin binding to rat small intestinal brush border vesicles was further investigated using structural analogues of riboflavin. The vesicles, prepared by Ca(2+)-precipitation, were incubated at 25 degrees C, for 20 min, in the presence of [3H]-riboflavin at physiological intraluminal concentrations for rat, and each analogue, at appropriate concentrations. Three groups of analogues were used, that were derived from the riboflavin molecule by modifying one of the following positions: the ribityl side chain, position 3, and position 8 of the isoalloxazine moiety. Group specificity was assessed by determining the inhibition potency of each analogue on the saturable component of riboflavin binding to the vesicles. Inhibition constants were calculated, according to Dixon, for lumiflavin, lumichrome, and for analogues substituted at position 8. Specific riboflavin binding was inhibited competitively by most of the analogues used. Substitutions at the ribityl side chain or at position 3 of the isoalloxazine moiety reduced the inhibition power. Substitutions at position 8 enhanced the inhibition power in direct proportion to the bulk of the substituents. We conclude that the ribityl side-chain and the NH group at position 3 are essential for recognition by the specific binding sites, whereas the methyl group at position 8 is important but not essential. The analogues that bind to specific membrane sites for riboflavin share specificity requirements with many riboflavin binding proteins, and are also good substrates for the intracellular phosphorylating enzyme flavokinase. Thus, the riboflavin-binding component in the membrane is likely to be a protein with high specificity. Cellular internalization of the membrane bound vitamin is probably achieved by phosphorylation of the vitamin bound to the inner side of the membrane.
Pancreas and kidney transplantation is performed in uremic IDDM patients to cure end-stage renal failure and diabetes. Seventy-two simultaneous kidney-pancreas transplantations were performed at our Institution between July 1985 and November 1994. All transplants were performed using heart-beating cadaver donors. The first 25 patients received 26 segmental pancreas according to Dubernard (KPS), whereas the last 46 patients received a whole, bladder-drained pancrea according to Sollinger (KPW). Mean pancreas cold and warm ischemia times were 294 +/- 14 and 44 +/- 2 minutes, respectively, in the KPS group and 660 +/- 37 and 40 +/- 8 minutes, respectively, in the KPW group. Twelve (48%) KPS patients and 19 (41%) KPW patients had postoperative pancreas surgical complications: vascular thrombosis led to graft failure in 5 KPS patients (20%) and 2 KPW patients (4%) (p = 0.01). Pancreatic fistula, hemorrhagic complications, and duodenum-bladder leakage were the surgical complications observed more frequently. Six KPS patients (24%) and 8 KPW patients (17%) underwent reintervention as a consequence of surgical complications. Fifteen KPS patients (60%) and 30 KPW patients (65%) experienced an acute kidney rejection episode, which was steroid-resistant in 14 KPW and 2 KPS patients. The actuarial survival rates for simultaneous kidney-pancreas recipients at one and 4 years were 92% and 84%, respectively, for KPS recipients, and 95% and 88%, respectively, for KPW patients. Kidney actuarial survival rates at one and 4 years were 96% and 76% respectively, for group KPS, and 93% and 89%, respectively, for KPW patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Six patients (3 children and 3 adults) with the clinical and biochemical features of Bartter's syndrome are presented. Pediatric cases included a more severe form, in one patient, with physical and mental retardation, hypercalciuria and nephrocalcinosis, and a less severe one, including two patients, with milder clinical features, low calcium and high magnesium excretion and hypomagnesiemia. Adult patients were affected by either the mild congenital form (case n. 4) or the acquired variety (cases n.5 and 6). Tubular function was investigated in the 3 adults by assessing clearance measurements during maximal diuresis. There was a defective fractional distal solute reabsorption (FDR) ranging between 0.52 and 0.60. This was well below the results obtained in one patient with psychogenous vomiting (FDR 0.94) and comparable to those in two patients with interstitial nephropathies caused by vesico-ureteral reflux (FDR 0.63 and 0.67 respectively). We concluded that: 1) the etiopathogenetic spectrum of Bartter's syndrome corresponds to different clinical presentation (mild, heavy, congenital or acquired varieties), and alterations in mineral and electrolyte renal handling; 2) reduction in FDR is a feature neither essential nor exclusive of this syndrome.
Neuroleptic malignant syndrome is a serious adverse reaction of neuroleptic drug therapy, composed of mental status changes, muscular rigidity, hyperthermia, signs of autonomic instability and typical laboratory findings. The syndrome has received increased attention in the scientific literature since 1980; nevertheless some weighty issues regarding clinical symptoms, etiopathogenesis and treatment require additional studies. This paper presents 9 cases of neuroleptic malignant syndrome prospectively observed in 8 inpatients and 1 outpatient with different psychiatric diagnosis. Levenson's diagnostic criteria were fulfilled in 7 cases; the remaining two had slighter symptoms. So neuroleptic malignant syndrome is to be considered a rare but not unusual side effect of neuroleptics. The risk of syndrome doesn't seem to be correlated with chemical class, D2 receptor affinity and total dosage of neuroleptics; a key factor seems instead to be a quick loading rate of neuroleptics. Seven of 9 cases displayed severe changes in mental status (clouding of consciousness that varies from stupor to coma), violent psychomotor excitement and aggressiveness before the onset of the syndrome. Such clinical features seem themselves, in our experience, to be potential risk factors besides reason for an increase of neuroleptic dosage. Neuroleptic malignant syndrome usually is preceded by prodromal signs, the most important appearing the worsening of alterations in consciousness. Symptoms of neuroleptic malignant syndrome usually appear abruptly and in some cases with a dramatic course; they last, in cases with favourable outcome, a few days to two weeks from neuroleptic withdrawal; by far the worst outcome, instead, occurs if diagnosis and drug discontinuation are not carried out early. The first measure in the treatment of neuroleptic malignant syndrome consists of prompt discontinuation of all neuroleptic medications and other psychopharmacological cures, except for benzodiazepines, and institution of supportive therapy; such interventions can resolve the most of cases. Three patients treated with bromocriptine and/or dantrolene didn't display a different duration of clinical symptoms and rate of complications if compared to patients treated with supportive therapy only. Use of bromocriptine or dantrolene, or both, therefore should be considered as a second line of action. In four cases, neuroleptics were reintroduced within few days of recovery; low potency neuroleptics were employed, given low doses which gradually increased: in none of the 4 cases did the patients experience partial or complete recurrence of neuroleptic malignant syndrome.
Myoglobin (Mb) is an intracardiac protein known to be rapidly released after onset of reperfusion. The new automated latex-enhanced nephelometric immunoassay is an interesting fast alternative to the other methods. Therefore we sought to assess the accuracy of rapid rise of Mb concentration to predict the success of reperfusion. Thirty consecutive patients, admitted to the coronary care unit for first acute Q-wave myocardial infarction, were prospectively studied. They underwent thrombolysis 126 +/- 45 min (range 30-180) after onset of symptoms. Mb determinations were obtained before starting therapy and, thereafter, hourly for 5 hours, and after 8 and 12 hours. The usual non invasive markers of reperfusion were considered, and coronary arteriography was performed in all patients at 5.5 +/- 0.9 days (range 1-6). In 23 patients (77%) patent infarct-related artery (IRA) (TIMI II-III) and in 7 (23%) occluded IRA (TIMI 0-I) was observed at coronary arteriography. We modified the judgment in 3 cases (10%) with occluded IRA. All reperfused patients (Group A) showed a rapid rise of Mb concentration with a mean time to peak occurring 133 +/- 80 min (range 60-180) after therapy. Mean value of unreperfused patients (Group B) was 330 +/- 173 min (range 180-420). We retrospectively stated a time to peak of Mb concentration within 180 min as diagnostic threshold for reperfusion. Sensitivity was 100%, specificity 50%, positive predictive value 93%, negative predictive value 100%. The results of this study confirm that Mb release kinetics may play an interesting role in the early prediction of patency of IRA in acute myocardial infarction after thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
The authors report a case of traumatic internuclear ophthalmoplegia and discuss its pathophysiologic mechanism. Internuclear ophthalmoplegia due to head trauma is uncommon, though it may be more common than reported since signs and symptoms typically resolve over weeks to months, and in multiple trauma patients other serious injuries overshadow disturbances of eye movements. A lesion involving medial longitudinal fasciculus was found by magnetic resonance imaging in the early post-traumatic period; this lesion was not seen when routine X-ray computed tomography was performed at the time of injury, confirming that magnetic resonance scanning is definitely superior to computed tomography for evaluating internuclear ophthalmoplegia.
Despite its shortcomings as a disease model, the chimpanzee is still the most relevant animal model for human immunodeficiency virus type 1 (HIV-1) infection. Previous studies have revealed qualitative differences between human and chimpanzee anti-HIV-1 responses. In this study, the development of specific anti-HIV-1 antibody-dependent cellular cytotoxic (ADCC) reactivities was evaluated in chronically infected chimpanzees and compared to the human response, because anti-HIV-1 ADCC represents a major component of anti-envelope cytolytic response found in infected patients. Ten HIV-1-infected chimpanzees up to 5 years after the infection were investigated. Anti-HIV-1 ADCC-directing antibodies were detectable in only three of 10 infected chimpanzees, and in these animals, activity was apparent only several months after the HIV infection. In some of the infected animals, ADCC reactivity against infected cells preceded reactivity against gp120-coated targets. When anti-gp120 ADCC-directing antibodies were apparent, they exhibited the same broad reactivity described in humans against different HIV isolates. The pattern of ADCC reactivities in infected chimpanzees is completely different from the well-characterized anti-gp120 cytotoxic reactivities present in HIV-1-infected patients. It is a relatively rare and late-occurring event that may have an important bearing on the lack of virus-induced pathogenesis in the chimpanzee model.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In 50 psychiatric inpatients treated with neuroleptics we observed neuroleptic-induced dysphoria in 4% and neuroleptic-induced akathisia in 18% of the cases. In our sample there was no schizophrenics among dysphoric responders. We discuss the implication of the findings and the relationship between dysphoric response and subjective phenomena of akathisia.
Peripheral blood lymphocytes obtained from a patient affected by adenosine deaminase (ADA) deficiency and severe combined immunodeficiency were infected with a retroviral vector containing two copies of a human ADA minigene, and injected into bg/nu/xid (BNX) immunodeficient mice. Six to 10 weeks after injection, human T cells were cloned from the spleens of recipient animals and analyzed for proliferative potential, T-cell surface markers, expression of ADA activity, integration of retroviral sequences, T-cell receptor (TCR) beta gene rearrangement, and specificity of antigen recognition. Efficient gene transfer and expression restored proliferative potential in vitro and long-term survival in vivo. All clonable human T lymphocytes obtained from the spleen of recipient animals had high levels of vector-derived ADA enzyme activity and showed predominantly the CD4+ phenotype. Retroviral integrations and TCR-beta gene rearrangements demonstrated the presence of a variety of different clones in the spleens of recipient mice. Furthermore, the combined analyses of vector integration and TCR rearrangement provided evidence that a circulating progenitor cell was transduced by the retroviral vector, giving rise to different and functional TCRs. Evaluation of antigen-specificity demonstrated both alloreactive and foreign antigen specific immune responses. These results suggest that restoration of enzyme activity in human ADA-deficient peripheral blood T cells by retroviral-mediated ADA gene transfer allows in vivo survival and reconstitution of specific immune functions. Therefore, retroviral vector-mediated gene transfer into circulating mononuclear cells could be successful not only in maintaining the metabolic homeostasis, but also for the development of a functional immune repertoire. This is a fundamental prerequisite for the usage of genetically engineered peripheral blood lymphocytes for somatic cell gene therapy of ADA deficiency.
The effect of aging on the intestinal transport of thiamin was studied using small intestinal microvillous vesicles prepared from groups of rats aged 1, 2, 6, 12 and 24 months, respectively. The vesicles (enrichment 14.6-17.8-fold) were incubated with 0.125 to 12.5 microM tritiated thiamin and the radioactivity taken up was measured radiometrically after rapid filtration. The time course and cumulative uptake curves of thiamin and the inhibiting potency of the thiamin structural analogs pyrithiamin, amprolium and oxythiamin on the saturable component of thiamin transport were determined. The vesicle diameter was measured by using a computerized morphometric procedure, and found to be decreased in aged rats. The Km and Jmax values of the saturable component of transport increased with increasing age, the difference with younger groups being statistically significant at 24 and 12 months. The inhibitory potencies of pyrithiamin and amprolium gradually decreased with increasing age, while oxythiamin was devoid of significant inhibitory activity. Passive permeability coefficients decreased with increasing age, reaching their lowest value at 24 months. These results show that aging is associated with intrinsic alterations of the enterocytic plasma membrane resulting in a decrease of the affinity for thiamin, associated with a faster rate of the saturable component of thiamin transport, and with a significant depression of the non-saturable component.