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Biomedical subjects

A Natale

Publications and source records attributed to A Natale.

At least 19 recordsLinked to original sources
PubMed1992

An anatomically guided approach to atrioventricular node slow pathway ablation.

Radiofrequency ablation of the "slow" pathway of the atrioventricular (AV) node reentrant circuit may be guided by electrophysiologic ("slow pathway potential") or anatomic landmarks. Experience with a systematic, anatomically guided approach in 25 patients (20 women and 5 men, aged 38 +/- 15 years) with typical AV node reentry is described. The slow pathway is assumed to be the posterior input to the AV node, approaching the nodal region in the corridor between the tricuspid annulus and the orifice of the coronary sinus. A series of radiofrequency lesions are given to interrupt this corridor at its entrance to Koch's triangle. If this is unsuccessful, the series of lesions are repeated progressively at higher levels approaching the AV node. The major end point for success is elimination of the slow pathway as determined by extrastimulus testing. A mean of 1.2 +/- 0.2 ablative sessions (20 +/- 12 applications of energy) achieved clinical success in 24 of 25 patients (96%) at a follow-up of 8.6 +/- 2.2 months. Anterograde Wenckebach cycle length increased from 361 +/- 67 ms to 398 +/- 70 ms (p = 0.01), yet the atrio-Hisian interval in sinus rhythm did not change (69 +/- 17 ms before vs 65 +/- 15 ms after ablation), p = 0.22. Retrograde Wenckebach cycle length was not affected (348 +/- 78 ms before vs 366 +/- 82 ms after ablation). During ablation, transient third-degree AV block occurred in 6 patients with no permanent sequelae. This approach provides a systematic, expedient technique to eliminate slow pathway conduction based on anatomic landmarks.

Adult↗
PubMed1992

Enhanced clearance of radiolabeled murine monoclonal antibody by a syngeneic anti-idiotype antibody in tumor-bearing nude mice.

A syngeneic anti-idiotype monoclonal antibody (MAb) (CM-11) directed against an anti-carcinoembryonic antigen (CEA) murine MAb (NP-4) was evaluated as a second antibody (SA) to promote the rapid clearance of radiolabeled NP-4 from the blood. Initial studies confirmed that CM-11 IgG removed 131I-NP-4 IgG from the blood as effectively as a polyclonal donkey anti-goat IgG removed 131I-goat IgG. However, use of an F(ab')2 in place of either the NP-4 or CM-11 IgG was not as effective in removing primary radiolabeled antibody, despite the formation of high-molecular-weight complexes. In accordance with previous results, the timing and dose of the SA injection was critical for optimizing tumor uptake and improving tumor/non-tumor ratios. In nude mice bearing GW-39 human colonic tumor xenografts, a delay in the injection of CM-11 by 48 hr after injection of radiolabeled NP-4 was optimal, since this allowed maximum tumor accretion. At a 200:1 CM-11:NP-4 ratio, tumor uptake was reduced, suggesting inhibition of NP-4 binding to CEA within the tumor. Despite optimizing tumor uptake by delaying SA injection and adjusting its dose, the percentage of 131I-NP-4 in the tumor decreased 2- to 3-fold within 2 days after CM-11 injection. A similar effect was seen for 111In-labeled NP-4 IgG with CM-11. Injection of excess unlabeled NP-4 given to block CM-11 shortly after its injection failed to curtail the loss of NP-4 from the tumor. Our results suggest that high blood levels of MAb are important for sustaining NP-4 in the tumor. Radiation-dose predictions derived from biodistribution studies indicate that a higher tumor dose may be delivered using the SA method than with either 131I-NP-4 IgG or F(ab')2 alone. Use of the SA method with 90Y-labeled NP-4 IgG, as modeled from biodistribution studies with 111In-NP-4 IgG, would likely be limited by liver toxicity.

Animals↗
PubMed1992

Importance of reperfusion on thromboxane A2 metabolite excretion after thrombolysis.

Fibrinolytic therapy is a major advance in the treatment of coronary artery disease. A marked elevation in plasma and urinary metabolites of thromboxane A2 (TXA2) after administration of thrombolytic therapy has been observed and has been related to a direct effect of thrombolytic drugs on platelets. To test this hypothesis we evaluated the 11-dehydro-thromboxane B2 (11-d-TXB2) level, as an index of platelet activation, in 20 healthy subjects and in 30 patients with acute myocardial infarction (AMI). Patients with infarction received streptokinase (n = 8), recombinant tissue-type plasminogen activator (rt-PA) (n = 8), or thrombolytic therapy preceded by acetylsalicylic acid (n = 7) or were treated without thrombolytic therapy (n = 7). The urinary 11-d-TXB2 level in healthy control subjects was 327 +/- 126 pg/mg creatinine. A significant increase was observed in patients with AMI with no difference between those who received no thrombolytic therapy (673 +/- 283 pg/mg creatinine in the first 12 hours) and those who received streptokinase (833 +/- 613 pg/mg creatinine) or rt-PA (836 +/- 653 pg/mg creatinine). Patients pretreated with acetylsalicylic acid had urinary 11-d-TXB2 values ranging between 361 and 155 pg/mg creatinine. A significant difference in 11-d-TXB2 values was observed only when patients who were reperfused were separated from those who remained occluded according to angiographic criteria (1085 +/- 498 vs 391 +/- 227 pg/mg creatinine in the first 12 hours, p less than 0.001). We conclude that reperfusion and not thrombolytic agents per se appears to be the factor that induces platelet activation and consequently facilitates reocclusion.

Aspirin↗
PubMed1992

Effects of acute and prolonged administration of propafenone on internal defibrillation in the pig.

Some antiarrhythmic sodium channel blocking drugs have been found to increase the energy necessary for internal defibrillation. Propafenone is a new drug that has been shown to be efficacious in the therapy of supraventricular and ventricular arrhythmias, and is of potential use in patients with defibrillators. The effects of short-term and prolonged propafenone administration on the internal defibrillation threshold (DFT) were determined in 43 pigs randomized to one of four groups: saline infusion (n = 10); propafenone infusion (n = 10); placebo administration for 8 days (n = 10); or propafenone administration for 8 days (n = 13). Two mesh electrodes were sutured on the right lateral and left lateral epicardial surface and current was delivered from the right electrode to the left electrode. Triplicate DFTs were obtained before and at 40 and 80 minutes after infusion of drug or placebo. In pigs receiving long-term administration, after baseline DFTs were obtained the electrodes were removed and the chest was closed. Following 8 days of drug or placebo administration, DFTs were redetermined. No changes were observed in the short- or long-term control groups. DFTs were lower after propafenone administration: either short-term infusion (20 +/- 6.2 joules at baseline; 15.6 +/- 5 joules at 40 minutes, p less than 0.05; 10.2 +/- 6 joules at 80 minutes, p less than 0.001) or long-term administration (17.8 +/- 2.6 joules at baseline versus 12 +/- 3.2 joules on drug, p less than 0.002). Decreased ventricular cycle lengths were found with acute administration of propafenone. Three pigs died during long-term administration of propafenone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Rapid blood clearance of immunoglobulin G2a and immunoglobulin G2b in nude mice.

An extremely rapid blood clearance rate of murine IgG2a antibodies was found in all strains tested of outbred Swiss nu/nu mice, including mice from the major commercial suppliers. The clearance half-life was less than 5 h, in comparison to a 4-5-day half-life in BALB/c mice. Therefore, most of the IgG2a antibody injected i.v. in such mice is cleared before it can reach interstitial fluid, which interferes with immunotherapy and immunodetection experiments. Individual nude mice varied greatly in their IgG2a clearance rates, which hampered investigation of the phenomena. In our experience, approximately three-fourths of nude mice had a rapid or intermediate clearance rate, whereas the remainder had an approximately normal clearance rate. The clearance rate in nude mice was age-dependent, at least in some instances, in that a rapid clearance rate was observed at 2 months of age, whereas the same mice retested at 4 months of age had a normal clearance rate. Rapid clearance could be inhibited by increasing the dose injected: 100 micrograms/mouse resulted in a normal clearance rate, whereas 30 micrograms/mouse was insufficient to inhibit rapid clearance. The clearance rate of IgG2b antibodies was affected similarly to that of IgG2a, whereas the clearance rate of IgG1 and IgG3 was not affected. The Fc region of IgG2a was required in order for rapid clearance to occur. Biodistribution experiments demonstrated that rapid blood clearance was due, at least partially, to binding to the liver and spleen. To determine the genetic basis for rapid IgG2a clearance, approximately 20 inbred and outbred mouse strains were tested. Unexpectedly, nu/+ as well as nu/nu outbred Swiss mice displayed rapid clearance, whereas control +/+ mice did not, so this phenotype appears to be a dominant effect of the nu mutation. BALB/c nu/nu and nu/+ mice did not display rapid clearance, which may be due to expression of the Igh-1a gene, which codes for the IgG2a present in BALB/c mice and in the monoclonal antibodies used in these studies. In conclusion, this clearance effect must be considered in experiments involving murine IgG2a or IgG2b antibodies in outbred Swiss nude mice, except those in which high antibody doses of greater than 0.1 mg/mouse are used. One method of circumventing this problem is to increase the antibody dose injected; a better but more long-range method is to develop strains of outbred nude mice that do have this characteristic.

Animals↗
PubMed1991

Successful radioimmunotherapy for lung metastasis of human colonic cancer in nude mice.

The potential for radioimmunotherapy as an adjuvant treatment for early disseminated colonic cancer was investigated in an experimental lung metastasis model. Nude mice receiving intravenous injection with a suspension of human colonic cancer cells (GW-39) developed multiple (10-100) tumor nodules throughout the lungs, and more than 50% of the animals died of extensive tumor involvement within 5-10 weeks. Groups of eight or nine animals bearing 7-day-old tumor transplants were treated with a single intravenous injection of radioiodinated agents: either 0.15 or 0.30 mCi of whole IgG of the NP-4 murine monoclonal antibody (MAb) against carcinoembryonic antigen (CEA) or 0.15 or 0.30 mCi of whole IgG of Immu-31, an anti-alpha-fetoprotein (anti-AFP) MAb. Treatment of animals with 0.15 or 0.30 mCi of 131I-labeled NP-4 IgG 7 days after injection of tumor cells resulted in survival for 23 weeks after tumor implantation in four of eight and seven of nine animals, respectively. Microscopic examination revealed that over 90% of the lung tumor colonies had no evidence of surviving cells. Animals treated with 0.30 mCi of anti-AFP, an irrelevant MAb, survived 4 weeks longer than controls. Toxicity was evident in four of the 17 animals given 0.30 mCi of NP-4 IgG (specific) or anti-AFP IgG (irrelevant) MAb. These animals died within 1-3 weeks after radioantibody injection, suggesting that death was related to the radiation dose. None of the animals given 0.15 mCi of 131I-MAb died within this period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

[Submucosal lipomas of the cecum. A case report].

The paper reports a case of submucous lipoma of the cecum. The difficulty of clinical diagnosis is underlined on account of aspecific symptoms, and in fact it is uncommon for diagnosis to be made on the basis of X-rays. Colonoscopy, in particular using bioptic techniques, allows the nature of the lipoma to be diagnosed, and in addition may act as an excellent therapeutic instrument.

Adult↗
PubMed1991

Effects of lidocaine on defibrillation threshold in the pig: evidence of anesthesia related increase.

Some antiarrhythmic drugs may influence the ability of a shock to defibrillate a patient but the effect of lidocaine on defibrillation efficacy has been controversial, suggesting multiple influencing factors. We determined the effects of three doses of lidocaine on defibrillation thresholds, using single and sequential shocks, in 36 open chest halothane-anesthetized pigs. An additional eight pigs were anesthetized with barbiturate and received the highest infusion regime of lidocaine. Shocks were delivered through three mesh electrodes sutured over the anterior right ventricle, posterior right ventricle, and lateral left ventricle for sequential pulse shocks and between a lateral right to a lateral left ventricular mesh electrode for single pulse shocks. Triplicate defibrillation thresholds (DFTs) were obtained before and after lidocaine (n = 32) or saline (n = 12) administration, either with halothane or barbiturate anesthesia. Lidocaine did not alter DFT at any dose with either the single pulse (control 17.4 +/- 3.7 joules [J], highest dose of lidocaine 13.5 +/- 1.7 J, P = NS) or sequential pulse shocks (control 7.6 +/- 0.8 J, highest dose lidocaine 6.6 +/- 0.7 J, P = NS), when halothane anesthesia was used. Similar results were obtained with lower doses. In contrast, lidocaine in pentobarbital anesthetized pigs produced a significant increase of the DFT with single (control 13.7 +/- 1.9, during lidocaine 16.6 +/- 3.1, P less than 0.01) and sequential shocks (control 11.1 +/- 2.2, during lidocaine 14.5 +/- 3.4, P less than 0.01). Interaction between barbiturates and lidocaine, and/or pH may account for the inconsistency in previous studies and must be considered for animal and clinical experiments.

Anesthesia↗
PubMed1991

[Right accessory pathway simulating a nodo-ventricular pathway: an electrophysiologic study and intraoperative mapping].

We report a case of a patient with episodes of wide QRS tachycardia and syncope. During the electrophysiologic study, a wide QRS tachycardia (200 b/m) with left bundle branch block morphology was reproducibly induced by incremental atrial pacing with progressive shortening of the HV interval and lengthening of the AV interval, suggesting the presence of a nodoventricular accessory pathway (Mahaim fiber). The intraoperative mapping performed during tachycardia showed the earliest ventricular activation to be over the right antero-lateral AV groove, different from the usual epicardial activation previously described. According to the earliest epicardial breakthrough point, we performed an epicardial AV fat pad dissection which produced irreversible disappearance of preexcitation, confirmed at the postoperative electrophysiologic study. No recurrence of tachycardia was observed during a follow-up of 11 months. This case further confirms previous data that the "so-called" Mahaim fibers could be a right accessory pathway with decremental properties.

Adult↗
PubMed1990

Masking level difference before and after surgery in unilateral otosclerosis.

The object of this paper was to evaluate the binaural hearing in 20 patients suffering from unilateral otosclerosis. Binaural performance was assessed at a test frequency of 500 Hz using masking level difference (MLD) before and after surgery. The postsurgical results showed abnormal MLDs in patients in whom stapedotomy had successfully corrected the threshold asymmetry. Three possible hypotheses regarding this phenomenon were investigated: (1) cochlear damage, (2) auditory deprivation and (3) a mechanical middle ear anomaly due to the surgical prosthesis or healing processes. The analyses suggest that the conductive hearing loss may effect central auditory processing resulting in poor binaural hearing (auditory deprivation theory).

Adult↗
PubMed1990

Opposite effects of propafenone and flecainide in a patient with reciprocating supraventricular tachycardia.

A 46 year-old woman with Wolff-Parkinson-White syndrome (postero-septal accessory pathway), symptomatic for recurrent episodes of nonsustained paroxismal supraventricular tachycardia (PSVT), was empirically treated with propafenone (600 mg/day). After a week of therapy the patient returned to the hospital after an episode of syncope. She referred a significant increase in duration and frequency of "palpitations". Under treatment with propafenone a sustained PSVT could be induced during transesophageal testing. During the electrophysiologic study performed off drugs, only a nonsustained PSVT could be induced. After flecainide infusion (1 mg/kg) anterograde block of the accessory pathway was observed and only few beats (less than 8) of PSVT could be induced. The patient was discharged on flecainide (200 mg/day) and 1 month later a transesophageal testing was repeated showing an anterograde block of the accessory pathway at a pacing cycle length of 500 ms; no arrhythmias were induced. The patient has been asymptomatic on chronic oral therapy with flecainide during a follow-up period of 8 months. This case shows that 2 1c class antiarrhythmic drugs may have opposite effects (proarrhythmic and antiarrhythmic). Failure, or even the proarrhythmic effect of one drug, does not necessarily exclude the efficacy of another drug of the same subclass in preventing recurrence of PSVT.

Administration, Oral↗
PubMed1990

[A case of primary lymphoma of the rectum].

The Authors describe a case of primary rectal lymphoma. The primitive involvement of this area is infrequent. The Authors emphasize the difficulty of preoperative diagnosis. The therapeutic approach should allow for correct staging which is only obtained by means of diagnostic studies aimed at excluding multicentric localisation. Sensitivity to radiotherapy has led the Authors to propose it as primary treatment, at least in stage I; surgery must be considered elective in stage II or in cases of need. Chemotherapy is indicated alone or in association with radiotherapy or surgery.

Aged↗
PubMed1989

Rhythm of carnitine levels in serum and urine of normal subjects.

A study of the diurnal serum and urine levels of L-carnitine and acetylcarnitine was carried out in eleven healthy volunteers. No significant difference was found between the levels in the morning and in the afternoon, although a higher carnitinaemia was shown in the waking hours when the energy demands were higher.

Acetylcarnitine↗
PubMed1988

Monocyte and polymorphonuclear leukocyte toxic oxygen metabolite production in multiple sclerosis.

Lipid-laden macrophages, which are predominantly derived from blood monocytes, are present at sites of active multiple sclerosis demyelination and are assumed to be involved in the demyelinating process. These inflammatory cells produce a variety of toxic oxygen metabolites which can mediate host tissue destruction. We measured production of two oxygen metabolites by monocytes and polymorphonuclear leukocytes in MS patients and controls. Stimulated monocytes produced significantly more hydrogen peroxide, superoxide, and chemiluminescence in the MS group than controls. The polymorphonuclear leukocyte, an inflammatory cell that appears to contribute little to MS demyelination, did not demonstrate increased production of toxic oxygen metabolites in the MS patients as compared to controls. These results suggest that blood monocytes in MS patients are primed to produce increased amounts of cytotoxic oxygen metabolites when exposed to inflammatory stimuli.

Humans↗