Ifosfamide and mesna in previously treated advanced epithelial ovarian cancer: activity in platinum-resistant disease.

PURPOSE: There is a critical need to find new antineoplastic drugs that are active in platinum-refractory ovarian cancer. We conducted a phase II trial of single-agent ifosfamide with mesna uroprotection in patients with ovarian cancer previously treated with an organoplatinum compound to assess its activity in this clinical setting. PATIENTS AND METHODS: Ifosfamide (1.0 or 1.2 g/m2/d for 5 days, delivered on a monthly schedule) was administered to the 57 patients entered onto this trial. Dose reductions were permitted for unacceptable toxicities. RESULTS: Toxicity included severe bone marrow suppression (WBC count less than 1,000/microL and/or platelet count less than 50,000/microL), renal dysfunction (serum creatinine level greater than 2.0 mg/dL), and reversible CNS dysfunction (disorientation, hallucinations, somnolence, and agitation), which occurred in 20%, 14%, and 12% of patients, respectively. Of 41 patients with strictly defined platinum-refractory ovarian cancer, five (12%) demonstrated a partial (four) or complete (one) response to this treatment program. CONCLUSION: Single-agent ifosfamide has modest but unequivocal activity in platinum-resistant ovarian cancer. Further studies of this drug used as a front-line agent along with an organoplatinum compound or as part of a dose-intensification program with bone marrow, peripheral stem cell, or colony-stimulating factor support are indicated. In addition, single-agent ifosfamide is a reasonable standard second-line treatment strategy in appropriately selected patients with platinum-refractory ovarian cancer.

Assessment of flow velocity reserve by transthoracic Doppler echocardiography and venous adenosine infusion before and after left anterior descending coronary artery stenting.

OBJECTIVES: We sought to evaluate whether coronary flow velocity reserve (CFR) (the ratio between hyperemic and baseline peak flow velocity), as measured by transthoracic Doppler echocardiography during adenosine infusion, allows detection of flow changes in the left anterior descending coronary artery (LAD) before and after stenting. BACKGROUND: The immediate post-stenting evaluation of CFR by intracoronary Doppler has shown mixed results, due to reactive hyperemia and microvascular stunning. Noninvasive coronary Doppler echocardiography may be a more reliable measure than intracoronary Doppler. METHODS: Transthoracic Doppler echocardiography during 90-s venous adenosine infusion (140 microg/kg body weight per min) was used to measure CFR of the LAD in 45 patients before and 3.7 +/- 2 days after successful stenting, as well as in 25 subjects with an angiographically normal LAD (control group). RESULTS: Adequate Doppler spectra were obtained in 96% of the patients. Pre-stent CFR was significantly lower in patients than in control subjects (diastolic CFR: 1.45 +/- 0.5 vs. 2.72 +/- 0.71, p < 0.01; systolic CFR: 1.61 +/- 1.02 vs. 2.41 +/- 0.68, p < 0.01) and increased toward the normal range after stenting (diastolic CFR: 2.58 +/- 0.7 vs. 2.72 +/- 0.75, p = NS; systolic CFR: 2.43 +/- 1.01 vs. 2.41 +/- 0.52, p = NS). Diastolic CFR was often damped, suggesting coronary steal in patients with > or =90% versus <90% LAD stenosis (0.86 +/- 0.23 vs. 1.69 +/- 0.43, p < 0.01). Coronary stenting normalized diastolic CFR in these two groups (2.45 +/- 0.77 and 2.64 +/- 0.69, respectively, p = NS), even though impaired diastolic CFR persisted in three of four patients with > or =90% stenosis. Stenosis of the LAD was better discriminated by diastolic (F = 49.30) than systolic (F = 12.20) CFR (both p < 0.01). CONCLUSIONS: Coronary flow reserve, as measured by transthoracic Doppler echocardiography, is impaired in LAD disease; it may identify patients with > or =90% stenosis; and it normalizes early after stenting, even in patients with > or =90% stenosis.

A study of high-index-contrast 90 degree waveguide bend structures.

We present an evaluation of the parameters involved in designing low-loss right-angle waveguide bends based on a high index contrast materials system. We apply the finite difference time domain method (FDTD) to several two-dimensional bend structures and study the effects of varying the bend geometry. Such a study is relevant for the understanding of bend mechanisms and for the optimization and fabrication of high-density high-contrast integrated optical components. The study indicates that high bend transmission can be achieved with the addition of a low- Q resonant cavity; however, similar or even better performance can be achieved with a structure that combines a corner mirror with a phase retarder. The use of a double corner mirror structure is shown to further increase the bend transmission, with little increase in bend area.

Peculiarities of prevalence and morphology of congenital heart disease detected in utero.

Intrauterine echocardiography is changing our knowledge of congenital heart disease; cardiac defects diagnosed in utero have distinctive features of both prevalence and morphology when compared with those observed just after birth. We reviewed a series of 171 fetal heart conditions: 148 were diagnosed at intrauterine echocardiography, the diagnosis being verified at autopsy in 41, and 23 were observed at the postmortem only. Peculiarities of prevalence consisted in an excess of various defects, such as hypoplastic left heart syndrome, atrial isomerism, pulmonary atresia, and atrioventricular and atrial septal defects, and in a reduced number of completely different conditions, such as transposition of great arteries and aortic coarctation. Differences in prevalence have been attributed to difficulties in diagnosing some particular anomalies in utero, to the selection of pregnancies undergoing screening, and to the special intrauterine evidence of some heart defects. Peculiarities in morphology result from the coexistence with extracardiac malformations, from the changes in shape conditioned by fetal hemodynamics, and from the intrauterine evolution of the morphology of some malformations. We concluded that the knowledge of these characteristic traits was helpful to cardiac pathologists, pediatric cardiologists, and obstetricians, and allowed the re-evaluation of the role of hemodynamic factors in remodeling the malformed cardiovascular appara-tus.

Met-enkephalin levels during PTCA-induced myocardial ischemia.

Met-enkephalin (Met-enk) has been demonstrated to modulate myocardial-ischemia mechanisms via the opioid receptors, but no studies are now available on Met-enk levels in the coronary circulation. In this experience Met-enk levels were evaluated in aortic root and in coronary sinus at baseline (T0), during PTCA induced transient ischemia (T1) and during reperfusion (T2). No significant differences were found at any time. Thus, it appears that there is no Met-enk extraction from the coronary circulation during provoked myocardial ischemia and no Met-enk release from the ischemic heart.

Left ventricular outflow tract obstruction in atrioventricular septal defects: a pathologic and morphometric evaluation.

Subaortic stenosis has been described with increasing frequency as an ominous feature of atrioventricular septal defect (AVSD), especially following surgical correction of the anomaly in non-Down's syndrome patients. In order to study the surgical anatomy of the left ventricular outflow tract in this malformation, 48 hearts featuring AVSD were examined. Obstructive lesions were classified into unequivocal forms (class A, 13.5%) and potential ones (class B, 10.8%). In the remaining hearts (class C, 75.7%) no obstruction was noted. In class A, subaortic stenosis was due to exaggeration of the anticipated anomalous arrangement of atrioventricular valve tensor apparatus, to the persistence of a subaortic muscular infundibulum, and to a discrete fibrous diaphragm. A potential for subaortic stenosis is provided by the unwedged position of the aortic valve. The left ventricular outflow tract is transformed into a long, forward-displaced fibromuscular channel. Morphometric analysis showed in AVSD (with both common annulus and separate orifices) a significantly (p less than 0.01) lower inflow/outflow tract ratio, and a significantly (p less than 0.01) lower right ventricular/left ventricular outflow length ratio than normal hearts. These results suggest that AVSD is characterized not only, as commonly stated, by inflow tract shortening, but by outflow tract lengthening as well. On these anatomical grounds, nearly all cases of AVSD could harbor the potential for subaortic stenosis; however, this becomes a real hazard (class B) only when associated with forward displacement of the left anterior papillary muscle, or direct insertion on the ventricular septum of the anterior bridging leaflet, and it may be converted to an actual obstruction by the effects of surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Salvage intraperitoneal therapy of advanced epithelial ovarian cancer: impact of retroperitoneal nodal disease.

PURPOSE: The objective of this study was to evaluate the impact of retroperitoneal lymph node disease on the efficacy of salvage intraperitoneal (IP) chemotherapy for advanced epithelial ovarian cancer. METHODS: We retrospectively reviewed the records of 41 patients with advanced epithelial ovarian cancer treated between 9/83-7/95, who had undergone retroperitoneal nodal sampling prior to salvage intraperitoneal chemotherapy. RESULTS: Of the 41 patients treated with debulking surgery and platinum-based chemotherapy, 19 (46%) had disease noted in retroperitoneal lymph nodes at initial surgery or at reassessment laparotomy, while 22 (54%) had biopsy-proven negative nodes. The mean age of the node-positive group was 49 years. Residual disease prior to initiation of IP therapy was optimal (< or = 2 cm) in 16 patients and suboptimal in 3. Twenty-two patients with a mean age of 55 were found to be node-negative. Residual disease prior to initiation of intraperitoneal therapy was optimal (< or = 2 cm) in all 22 patients. All patients received salvage intraperitoneal chemotherapy. With a median follow-up of 26 months since surgical reassessment, the median survival in the node-positive group is 31 months compared to 40 months for the node-negative group (p = 0.47). CONCLUSIONS: The presence of retroperitoneal nodal disease does not appear to be a contraindication to the use of salvage IP chemotherapy in advanced ovarian cancer.

Imaging of the posterior descending coronary artery. The last frontier in echocardiography.

BACKGROUND: Non-invasive color Doppler imaging of the left anterior descending coronary artery has been described, but imaging of the posterior descending coronary artery (PD) has never been reported. The aim of this paper was to describe color Doppler imaging and flow reserve of the PD, regardless of its origin from the right or circumflex coronary artery, in different settings such as acute myocardial infarction or coronary stenting. METHODS: A C256 Acuson Sequoia ultrasound system connected to a standard 3.5 MHz transducer was used. Neither a contrast agent nor harmonic or power Doppler imaging was used. However, the Nyquist limit of color Doppler was reduced to 12 cm/s. Patients were examined in the apical 2-chamber view, with the coronary sinus ostium imaged in the short axis until a diastolic flow signal close to the epicardial layer was detected. Pulsed Doppler confirmed an anterograde, doming systolic and monophasic decrescendo diastolic flow. Adenosine was intravenously infused at the standard dose of 140 microg/kg/min over 90 s in order to elicit maximal microcirculatory dilation. The resting and hyperemic peak diastolic flow velocities were measured and the coronary flow reserve was calculated as the ratio between hyperemic and resting peak diastolic flow velocities. RESULTS: This simple bedside technique provided crucial information about several important issues: 1) arterial patency after thrombolysis; 2) evaluation of the physiologic impact of a coronary stenosis, with implications on the detection of a critical stenosis; 3) reperfusion imaging of perforating branches after myocardial infarction; 4) post-stent assessment of coronary flow reserve. CONCLUSIONS: This paper shows, for the first time, that non-invasive imaging of the PD by non-contrast transthoracic Doppler is feasible and that the coronary flow reserve is measurable even in critical conditions. More studies are needed to assess the feasibility of PD imaging in different clinical settings and the potential benefit of contrast agents in improving the evaluation of coronary flow.

Non-invasive assessment of coronary flow velocity reserve before and after angioplasty in a patient with mammary graft stenosis.

We report the diagnosis of mammary artery graft dysfunction by high-resolution transthoracic Doppler and venous adenosine infusion. The patient was treated by percutaneous balloon angioplasty, with optimal angiographic results. Coronary flow reserve in the distal left anterior descending artery was abnormal before angioplasty, and recovered soon after the procedure. The utility of this new non-invasive technique in the diagnosis of flow-limiting stenoses and follow-up of coronary angioplasty is described.

Rheumatic fever recurrence: a possible cause of restenosis after percutaneous mitral valvuloplasty.

BACKGROUND: We evaluated the occurrence of a rapid process of restenosis after percutaneous mitral valvuloplasty (PMV), initiated by the recurrence of acute rheumatic fever. Restenosis after PMV has been mainly related to a high echocardiographic score (> or = 8) indicating a severely compromised mitral valve apparatus. METHODS: From 1986 to 1996, 120 patients underwent PMV by the transseptal approach at our Institution. The mean follow-up time was 58 +/- 32 months (range 3 months to 9 years). RESULTS: Restenosis occurred in 10 patients (8.3%): in 4 restenosis was found within a relatively short period of time (1 to 3 months) following a documented recurrence of acute rheumatic fever; in the other 6 patients there was a gradual loss of the initial gain in the mitral valve area. CONCLUSIONS: These data suggest two potential mechanisms of restenosis: 1) a more common slow process, due to turbulent flow-trauma on the mitral valve; 2) a rapid process that relates to valvulitis consequent to a recurrence of acute rheumatic fever. In consideration of the second possibility, after PMV prophylactic treatment may be warranted at least in those patients who are at high risk of streptococcal infection.

[Immunosuppressive therapy of vasculitis: current aspects and perspectives]. / Terapia immunosoppressiva delle vasculiti. Attualità e prospettive.

Vasculitides are a set of serious diseases of unknown aetiology with various immunopathogenetic mechanisms, characterized by inflammation and necrosis of the vessel wall with consequent lumen obliteration. They may be primitive or associated with other diseases, have heterogeneous clinical manifestations and different degrees of severity which may be related to the localization of the interested vessels. Although in the last years many classifications have been proposed, a standardized nomenclature of vasculitides is unquestionably still needed to facilitate the diagnosis and management of patients with the disease. Steroids and immunosuppressant are the conventional therapy, whereas other therapeutic strategies are reserved for the refractory vasculitides to conventional therapies or for intolerant recipients to cytotoxic drugs. New approaches are represented by monoclonal antibodies and drugs which could be effective in the treatment of the trigger factors which activate the immunopathological mechanisms. Current data suggest that, rather than pursuing the idea of a single therapy for vasculitides, an oncological model of combined therapy, to induce both the disease control and maintenance of remission, might be adopted. An improvement of our knowledges on the mechanisms underlying the different entities associated to standardized criteria of activity and remission of disease will lead to an improvement of our therapeutic strategies.

[The expansion of NK CD56+ cells with reduced cytotoxicity in a female patient with systemic sclerosis]. / Espansione delle cellule NK CD56+ con ridotta citotossicità in una paziente affetta da sclerosi sistemica.

An absolute and relative increase of circulating CD56+ (NKH1, Leu19) natural killer cells has been found in a patient with systemic sclerosis. The expanded natural killer cells exhibited reduced natural killer activity and antibody-dependent cell-mediated cytotoxicity. Furthermore, the limiting dilution analysis of spontaneous in vitro immunoglobulin synthesis demonstrated that the precursor frequency of immunoglobulin-secreting cells and the "single-hit" kinetics of the titration curve were similar to healthy controls, but strongly different from previously reported patients in whom CD16+NK cell subset was expanded. Thus, our findings might suggest that expanded CD56+ natural killer cells exhibit unique regulatory properties on B cell function in systemic sclerosis.

[Proposal for a nutritional study using a survey of anthropometric data on school-age children from the Molise countryside]. / Proposta di uno studio nutrizionale mediante il rilevamento dei dati antropometrici di bambini in età scolare nell'interland molisano.

The present work is a preliminary study, preceding a larger one in the Molise countryside ; its aim is to set out methodological and operative basis to estimate the nutrition state of children aged 6-10 years, through a survey of anthropometric data. The list of considered parameters is here related. From the analysis of the different parameters it comes out that the tested population shows a trend to have a body weight too high compared to its height. That involves a more thick-set and less long-limbed body structure. Although the sample is small in number, the results enable us to believe that carrying on the study on a vast scale is suitable.

[Validity of some electrocardiographic criteria in left ventricular hypertrophy]. / Validità di alcuni criteri elettrocardiografici di ipertrofia ventricolare sinistra.

The aim of the study was the assessment of the sensitivity, specificity and accuracy of some ECG criteria of left ventricular hypertrophy (LVH). Left ventricular mass (LVM) measured on the M-mode echogram of the left ventricle was the reference standard. Ninety-four (94) unselected, consecutive clinical patients (34 women, 60 men, average age 47 years) underwent in the same day, ECG and echocardiogram. Exclusion criteria were the presence of ischemic heart disease, atrial fibrillation and Wolff-Parkinson-White syndrome. The ECG tracings were interpreted independently by 2 investigators following 5 independent criteria of LVH: 1) Sokolow-Lyon voltage criterion (SL); 2) a modified Romhilt-Estes point score (REM); 3) left atrial abnormality (LAA); 4) left ventricular strain; 5) a new voltage criterion RaVL + SV3 corrected by sex and age. The left ventricular M-mode echograms were recorded using a left parasternal approach and were interpreted independently by 2 investigators. LVM was measured using the "Penn convention" and taking the R wave peak as end-diastole. The prevalence of LVH (= LVM 215 g) in the study population was 47%. The following results were achieved (sensitivity, specificity, accuracy): SL: 68.2%, 84%, 76.6%; REM: 63.6%, 90%, 77.7%: LAA: 36.4%, 84%, 61.7%; strain 52.3%, 72%, 62.8%; RaVL + SV3: 54.5%, 82%, 69.1%. Our data suggest: 1) the high sensitivity, specificity and accuracy of Romhilt-Estes point score are confirmed; 2) the sensitivity of Sokolow-Lyon voltage criterion is reevaluated; 3) the most sensitive morphological criterion seems to be the left ventricular strain; 4) a new voltage criterion could be useful.

[Rhabdomyoma of the left atrium. A rare case of mitral valve congenital obstruction simulating hypoplastic left heart syndrome. Echocardiographic diagnosis]. / Rabdomioma dell'atrio sinistro. Rara causa di ostruzione congenita della mitrale simulante sindrome del cuore sinistro ipoplasico. Diagnosi ecocardiografica.

The AA. describe the clinical, surgical and pathological features of a 13-days old infant with multiple cardiac rhabdomyomas diagnosed by two-dimensional echocardiography (2DE). The clinical picture simulated hypoplastic left heart syndrome (HLHS). 2DE showed a well developed left heart. The apical four chamber view disclosed a mass of echoes between the left atrium and ventricle, across the mitral valve. Another little mass of echoes was attached to the left surface of the ventricular septum. The other cardiac chambers and the great arteries were normal. These multiple intracardiac masses were interpreted as rhabdomyomas. The infant underwent an operation at the age of 21 days because of mitral valve obstruction and CHF. At surgery, a left atrial rhabdomyoma was found, that severely obstructed the mitral valve orifice. Although after resecting the tumour we felt that the obstruction was adequately relieved, the little patient died of pulmonary oedema one hour after surgery. At autopsy all the previously detected myomas were confirmed and a small additional one was discovered within the crista supraventricularis. Unexpectedly, the chordae tendineae of the mitral valve were extremely short. This anomaly, masked preoperatively by the rhabdomyoma, was probably the cause of the fatal postoperative mitral regurgitation.

Prenatal echocardiographic diagnosis of right atrial isomerism.

A prenatal diagnosis of right atrial isomerism is often inferred through the recognition of a constellation of cardiac anomalies on the four-chamber view or by the detection of visceral heterotaxy and asplenia. However, the actual occurrence of discordance between the arrangement of the atria and thoracic and abdominal organs makes the identification of the morphology of both atrial appendages the only reliable way to make a final diagnosis of atrial isomerism. Three cases of right atrial isomerism with visceral heterotaxy and a complex cardiac defect, diagnosed in utero by cross-sectional and colour flow Doppler echocardiography, are reported. In all the patients, the right atrial isomerism was associated with an atrioventricular septal defect, a single aortic outlet from the right ventricle, and total anomalous venous return. The diagnosis of right atrial isomerism, always confirmed by neonatal re-evaluation and/or by post-mortem examination, was made through identifying two pyramidal atrial appendages in an echocardiographic transverse plane at the level of the atria and of the origin of the great arteries. This report demonstrates that a final intrauterine diagnosis of atrial isomerism is possible, whatever the visceral situs is.

[Hypertrophic obstructive cardiomyopathy associated with significant coronary artery stenosis. Apropos of 2 cases. Diagnostic and therapeutic considerations and review of the literature]. / La cardiomiopatia ipertrofica ostruttiva associata a stenosi significative delle arterie coronarie. A proposito di due casi. Considerazioni diagnostiche e terapeutiche, a revisione della letteratura.

Hypertrophic obstructive cardiomyopathy (HOCM) is rarely associated with significant coronary artery stenosis. Differential diagnosis may be difficult because of similar symptoms; therefore we suggest coronary arteriography in all patients above 30 years of age having HOCM and angina associated. Obviously, in case the clinical diagnosis is coronary artery occlusive disease, left ventriculography is mandatory to rule out HOCM. Four medical treatment beta-blocking agents are the drugs of choice associated, if needed, with coronary dilators, avoiding nitrates. In case surgical treatment is selected, complete correction of all lesions is indicated.

Angulated transverse tomographic sections to measure cardiac dimensions by magnetic resonance imaging: a comparison with 2D-echocardiography.

Magnetic resonance imaging (MRI) has shown low accuracy in measuring cardiac dimensions in normal subjects, when transverse tomographic sections are used in comparison with 2D-echocardiography. The rationale of this study was to compare cardiac dimensions in 19 volunteers based on angulated (30 degrees caudo-cranial) transverse tomographic sections both in MRI and 2D-echo. Since the planes investigated by both techniques are superimposable, highly significant correlated Ao, LA, IVS, LW, LV, and RV dimensions are observed. Standardized MRI tomography permits reduction of total examination time and assures repeatability. Thus, using the method reported here, cardiac dimensions in humans might be obtained accurately by MRI.