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Biomedical subjects

P Ferrazzi

Publications and source records attributed to P Ferrazzi.

At least 19 recordsLinked to original sources
PubMed2004

Percutaneous bridge to heart transplantation by venoarterial ECMO and transaortic left ventricular venting.

We report a case in which life support for cardiogenic shock was achieved by a nonpulsatile venoarterial bypass, and left ventricular decompression was obtained by a catheter placed percutaneously through the aortic valve into the left ventricle. The blood drained from the left ventricle was pumped into the femoral artery. The normalization of left heart filling pressures allowed the resolution of pulmonary edema, and the patient underwent a successful heart transplantation following 7 days of mechanical cardiocirculatory support.

Adult↗
PubMed2001

Mitral valve repair and transesophageal echocardiographic findings in a high-risk subgroup of patients with active, acute infective endocarditis.

BACKGROUND AND AIM OF THE STUDY: Limited data are available regarding the efficacy of mitral valve repair in patients affected by active, acute infective endocarditis. In addition, the predictivity of transesophageal echocardiography (TEE) for guiding the surgical decision-making process in these patients has not yet been reported. The study aim was to evaluate the long-term results of mitral valve repair and role of TEE in active, acute infective endocarditis. METHODS: The study population consisted of patients affected by infective endocarditis of the mitral valve who underwent surgery. TEE was performed intraoperatively to guide the best surgical approach. All patients were followed up (mean 73+/-8 months) after surgery. RESULTS: Twenty-eight patients underwent surgery for infective endocarditis; of these, 13 had mitral valve repair for active, acute infective endocarditis and formed the basis of the study. Sensitivity, specificity, positive predictive value, negative predictive value of TEE in detecting the mechanism of mitral regurgitation were 87%, 100%, 100% and 92%, respectively. The predictivity test of TEE in guiding surgical strategy was 94%. All patients were alive at the time of follow up; 10 (77%) were in NYHA class I and three in class II (23%). Mitral regurgitation was severe in one patient (8%), moderate in three (23%), mild in four (31%), and absent in five (38%). No relapses of active infective endocarditis were observed during the follow up period. CONCLUSION: Mitral valve repair appears to be an effective treatment for active, acute infective endocarditis with mitral regurgitation and should be considered as a therapeutic strategy when surgery is contemplated. TEE has a fundamental role in the surgical decision-making process in these patients.

Acute Disease↗
PubMed2000

A study of iodothyronine 5'-monodeiodinase activities in normal and pathological tissues in man and their comparison with activities in rat tissues.

The present study was undertaken to investigate the peripheral iodothyronine 5'-monodeiodination in different human and rat tissues. We studied iodothyronine 5'-monodeiodinase type I (5'-DI) activity in liver, kidney, intestine, right cardiac atrium and skeletal muscle and we compared the results with those in rat tissues. Lodothyronine 5'- monodeiodinase type II (5'-DII) activity was studied in normal and ischemic human heart and in rat normal myocardium and brain. The 5'-DI activity (fmol/min x mg protein) in liver and kidney was significantly higher (p < 0.001, ANOVA) in normal rat tissue than in human. However, no significant differences were observed in 5'-DI activity between normal and tumoral human intestine or between intestinal tissue of man and rat. 5'-DI activity in normal human skeletal muscle was significantly higher than that in rat skeletal muscle (p < 0.05). The 5'-DI activity was lower in human ischemic myocardium when compared to normal myocardium either in humans (p < 0.05) or rat (p < 0.001). The Km of 5'-DI was significantly lower in rat than in human kidney and liver (p < 0.05). We conclude that 1) 5'-DI is distributed widely among extrathyroidal human and rat tissues and 5'-DII activity is detectable both in human and rat heart; 2) 5'-DI activity in liver and kidney is lower in man than in rat; 3) 5'-DI activity in the skeletal muscle is higher in man than in the rat; 4) 5'-DI activity is decreased in tumoral tissues of human liver and kidney and in ischemic myocardium, while no significant difference was found between human and rat cardiac 5'-DII activity.

Aged↗
PubMed2000

Measurement of brain natriuretic peptide in plasma samples and cardiac tissue extracts by means of an immunoradiometric assay method.

We evaluated the analytical characteristics and clinical usefulness of a commercial immunoradiometric assay (IRMA) kit for brain natriuretic peptide (BNP). Mean (+/-SD) plasma BNP concentrations measured in 129 normal subjects were 2.9+/-2.7 pmol/l (median 2.2 pmol/l; range 0.1-12.4 pmol/l). The mean (+/- SD) value observed in healthy men (2.1 +/- 2.0 pmol/l, n = 49) was significantly (p=0.0009) different to that found in women (3.4 +/- 2.9 pmol/l, n=80). A positive relationship (R=0.214, p=0.0174) was found between BNP values and age. In 65 patients with cardiac diseases, BNP levels increased with the progression of clinical severity of disease; patients with more severe disease [NYHA functional class III-IV, mean (+/- SD) BNP +/- 254 +/- 408 pmol/l, n=22] showed significantly (p<0.0001) increased values compared to patients with mild symptoms of disease (NYHA functional class I-II, mean (+/- SD) BNP=19.6 +/- 17.2 pmol/l, n=43). Furthermore, in 32 patients with chronic renal failure, greatly increased (p<0.0001) BNP values were found both before (mean +/- SD=88. 1+/- 111.1 pmol/l) and after haemodialysis (mean +/- SD=65.6 +/- 76.7 pmol/l), with a significant reduction after haemodialysis (p=0.0004) compared to pre-haemodialysis. The mean (+/- SD) BNP value found in atrial extracts collected during aorto-coronary bypass operations in 15 patients was 14.5 +/- 51.9 pmol/g of cardiac tissue. Moreover, the mean (+/- SD) tissue levels of BNP in 7 heart transplant recipients were 128.4 +/- 117.2 pmol/g of cardiac tissue in atrium, 68.4 +/- 76.7 pmol/g in ventricle, and 10.9 +/- 8.5 pmol/g in interventricular septum. Finally, BNP values found in cardiac tissues of two subjects collected at autopsy were considerably lower (on average 1/1000) than those observed in cardiac tissues of patients with cardiac diseases. The IRMA method for BNP determination evaluated in this study showed a good degree of sensitivity, precision and practicability. Therefore, this method should be a reliable tool for the measurement of plasma BNP levels for both experimental studies and routine assay.

Adult↗
PubMed1998

Preoperative assessment of coronary artery disease in aortic stenosis: a dipyridamole echocardiographic study.

BACKGROUND: The aim of this study was to establish the feasibility, safety, and diagnostic accuracy of the dipyridamole echocardiography test in patients with severe aortic valve stenosis for noninvasive detection of coexisting coronary artery disease. METHODS: The high-dose dipyridamole echocardiography test was performed in 52 patients with severe aortic stenosis; all patients also underwent coronary angiography, independent of test results, before cardiac operation. RESULTS: The dipyridamole echocardiography test was completed without major complications. One patient had transient atrial fibrillation that was reversed by aminophylline. Thirty-one patients (60%) had a negative test result; all had normal coronary arteries. Ten of the 21 patients (48%) with a positive test result had coexisting coronary artery disease. The positive predictive value of the dipyridamole echocardiography test for detection of coronary disease in patients with severe aortic stenosis was 48%. The negative predictive value was 100%. The sensitivity was 100% and the specificity was 74%. CONCLUSIONS: Dipyridamole echocardiography is a safe and feasible tool in patients with severe aortic stenosis eligible for a cardiac operation. A negative test result reliably rules out a significant stenosis, whereas a positive one is much less accurate in predicting coronary artery disease.

Aortic Valve Stenosis↗
PubMed1997

The risk of coronary artery disease after heart transplantation is increased in patients receiving low-dose cyclosporine, regardless of blood cyclosporine levels.

BACKGROUND: Coronary artery disease (CAD) of allografted hearts is the main cause of late mortality after cardiac transplant, but its etiology is still undetermined. HYPOTHESIS: This study was undertaken to evaluate the relevance of several risk factors, including cyclosporine (CsA) dose and blood CsA levels, to the incidence of CAD. METHODS: In 163 heart transplants performed between November 1985 and August 1994 at our Institution, CAD was diagnosed by coronary angiography or at postmortem examination. Patients in whom postmortem examination or coronary angiography was not performed, as well as those < 15 years of age and those who died within 1 month of surgery, were excluded from the study. The following risk factors were analyzed: recipient age, gender, pretransplant diagnosis, donor age, number of human leukocyte antigen (HLA)-AB mismatches, cytomegalovirus serology, mear serum cholesterol and triglyceride levels, the number of treated acute rejections, mean weighted CsA dose (CsA dosew and weighted blood CsA levels (blood CsA levelw). RESULTS: Coronary artery disease was diagnosed in 32 patients (19.6%). A low mean CsA dosew was the only significant predictor for CAD at multivariate analysis (p < 0.01): there was no correlation with blood CsA levelw. In the patients receiving a CsA dosew > 4 mg/kg/day, the 8.9 year probability of their remaining CAD free was 69% [confidence interval (CI) 50-87%] in comparison with 31% (CI 0-65%) in patients receiving a CsA dosew < 4 mg/kg/day. CONCLUSION: In our experience, a low CsA maintenance dose is the main risk factor for CAD, irrespective of blood CsA levels.

Adolescent↗
PubMed1996

Acute enoximone effect on systemic and renal hemodynamics in patients with heart failure.

Patients with heart failure generally show improvement in their clinical condition after enoximone infusion over the period of treatment; this effect cannot be ascribed only to the known hemodynamic action of this drug. Thirty-six patients (age range 44-82 years) with heart failure (NYHA class II-IV) underwent 48-hour enoximone infusion to study whether this prolonged improvement might depend on changes in systemic or renal hemodynamics or in neurohormonal balance. All patients underwent Swan-Ganz hemodynamic monitoring; renal plasma flow, glomerular filtration rate, plasma atrial natriuretic factor (ANF), and plasma renin activity (PRA) were all measured at baseline, at the peak of the enoximone action, and 48 hours after drug discontinuation. The main hemodynamic parameters were significantly improved during enoximone infusion and after drug discontinuation. The cardiac index basal value of 2.2 +/- 0.1 l/min/m2 increased to 3.1 +/- 0.1 l/min/m2 after 24-hour therapy (p < 0.01); similarly, pulmonary wedge pressure, mean pulmonary arterial pressure, and right atrial pressure decreased markedly (p < 0.01). Beneficial effects were also observed in renal hemodynamics; indeed, renal plasma flow (basal value 485 +/- 39 ml/min) increased significantly after 24-hour enoximone infusion (575 +/- 35 ml/min; p < 0.01), and this tendency was also observed 48 hours after drug discontinuation. No significant modifications were observed in plasma hormone data; however, the PRA plasma level had a tendency to decrease. We conclude that in patients with heart failure, enoximone infusion has a less marked effect on renal hemodynamics, but this is more lasting than systemic hemodynamic effects. The tendency of PRA to decrease (although not statistically significant), still detectable 2 days after treatment in the presence of steady high plasma ANF concentrations, may also contribute to the paradoxical longlasting benefit despite the short-lived improvement in systemic hemodynamics after brief cycles of enoximone infusion.

Adult↗
PubMed1996

Medical treatment of end-stage heart failure.

Congestive heart failure is a lethal condition that affects an increasing number of patients. In recent years a great amount of data have accumulated on the pathophysiology and medical and surgical therapy of this condition. In spite of the advances in its management and the great number of patients affected, common errors are still made by internists and cardiologists in the use of drugs and therapeutic strategies. Digitalis has only recently been shown to affect hemodynamics, exercise capacity, and clinical symptoms, but the effects on survival still have to be demonstrated. Loop diuretics, eventually combined with thiazides and antialdosterone drugs in patients with clinical signs and symptoms of fluid retention, are the mainstays of therapy of congestive heart failure. In order to make diuretic therapy efficacious, moderate salt and water intake restriction is mandatory. Angiotensin-converting enzyme (ACE) inhibitors are now considered unavoidable drugs in the management of heart failure, and an attempt to reach the doses that have been shown to be efficacious for survival in the large trials has to be made in every patient with this condition. Other vasodilators, such as hydralazine and nitrates, which show a less pronounced effect on survival but more effective hemodynamic actions than ACE inhibitors, may be used to control mitral insufficiency or to improve hemodynamics in very sick patients. Hemodynamic instability refractory to increasing doses of vasodilators and diuretics is a severe condition that requires hospital admission to administer drugs parenterally. These patients are usually treated with the combination of catecholamines and phosphodiesterase inhibitors associated with intravenous diuretics until clinical stability is again achieved and oral therapy is resumed and restructured. The use of aggressive pharmacological therapy and phosphodiesterase inhibitors has reduced the need for assisted circulatory support in these patients. Beta-blockers have shown promising results when administered to patients with heart failure, although a definitive demonstration of their effects on survival is still lacking. Other additional measures that need to be considered in patients with end-stage congestive heart failure are the use of antiarrhythmic drugs and anticoagulation.

Adrenergic beta-Antagonists↗
PubMed1995

Preliminary results of intrathymic injection of donor cells to prevent acute rejection in human heart transplantation.

In rodents, the intrathymic injection of donor cells or major histocompatibility complex peptides induces indefinite survival of a subsequent allograft with little or no immunosuppression. Here, experiments have been performed in two patients with cardiac transplantation to establish (1) the safety and tolerability of the intrathymic injection of donor leukocytes at the time of transplant surgery and (2) whether conventional immunosuppression interfered with the process of the thymic recognition of alloantigens. It was shown that the intrathymic inoculation of donor cells is safe and can be done without undesired effects. However, the procedure, as performed, did not protect from acute graft rejection. There are data enough to attribute the failure of the thymus technique in these two patients to the concomitant use of immunosuppressants. The results of this study are relevant for future trials aimed at finding the appropriate experimental conditions for the use of the thymic approach in human organ transplantation.

Acute Disease↗
PubMed1995

Reduction of haemorrhagic complications during mechanically assisted circulation with the use of a multi-system anticoagulation protocol.

Two different anticoagulation protocols were used in 49 consecutive patients mechanically supported either for bridge to transplantation (11) or for recovery of myocardial function after cardiac surgery (35). In 46 patients a Biomedicus centrifugal pump was used and in 3 patients a Pierce-Donachy ventricles. Mechanical support was provided to the left ventricle in 14 patients, to the right ventricle in 6 and to both ventricles in 12 patients; an extra-corporeal membrane oxygenator (ECMO) support was used in 17 patients. Thirty-seven males and 12 females, aged 0.2 to 58 years, were supported for an average time of 6.3 days (range 1-43). Anticoagulation was either based on a continuous infusion of heparin in the first 27 patients (group A) or on a multi-system therapy ("La Pitié" protocol) in the other 22 patients (group B). Overall survival rate was 47%. Patients in group A had a 30% (8/27) survival rate, whereas in group B a 68% (15/22) survival rate was observed (p = 0.006). Transplantation and ventricular assist device (VAD) removal was successfully obtained in 59% (16/27) and 91% (20/22) of patients in group A and group B respectively (p = 0.05). Significant bleeding occurred in 21 patients (81%) in group A and in 2 (9%) of group B (p = 0.001). In these patients bleeding averaged 230 +/- 231 ml/kg in group A versus 55 +/- 18 ml/kg in group B (p = 0.001). Surgical revision was necessary for cardiac tamponade or persistent bleeding in 12 patients of group A (25 procedures: mean 0.9/patient) and in 3 patients of group B (one each patient: mean 0.1/patient) (p = 0.01). Infection, thrombo-embolism and brain hemorrhage were also less frequent in group A than in group B. Our data suggest that the "La Pitié" protocol provides a better control of bleeding than the conventional heparin infusion in patients receiving assist device. this reduction in thrombo-hemorrhagic complications might improve the results of mechanical circulatory support.

Adolescent↗
PubMed1994

Following an initial decline, glomerular filtration rate stabilizes in heart transplant patients on chronic cyclosporine.

We previously reported that heart transplant patients given cyclosporine for more than 2 years (short-term evaluation) had severe renal lesions and markedly reduced glomerular filtration rate and renal plasma flow (Kidney Int 40:243-250, 1991). We report the analysis of renal function in the same patients after 3 additional years of follow-up (long-term evaluation) while they continued to take cyclosporine. Since the previous evaluation, the dose of cyclosporine was adjusted to maintain stable trough levels and antihypertensive therapy was unchanged. The mean time-averaged dose of cyclosporine during the follow-up was 4.5 +/- 2.1 mg/kg/d. The systolic blood pressure at long-term evaluation (146 +/- 16 mm Hg) was increased (P < 0.05) compared with that at short-term evaluation (140 +/- 13 mm Hg), whereas diastolic blood pressure (long-term 91 +/- 9 mm Hg v short-term 88 +/- 9 mm Hg) and mean blood pressure (long-term 110 +/- 12 mm Hg v short-term 108 +/- 11 mm Hg) did not change significantly. Serum creatinine concentrations at long-term (1.7 +/- 0.3 mg/dL) and at short-term (1.7 +/- 0.4 mg/dL) evaluations were similar. At long-term evaluation the renal plasma flow (300 +/- 64 mL/min/1.73 m2) was not decreased compared with that at short-term evaluation (325 +/- 94 mL/min/1.73 m2), while the glomerular filtration rate increased significantly (43 +/- 15 mL/min/1.73 m2 v 36 +/- 8 mL/min/1.73 m2, respectively; P < 0.05). None of the patients became proteinuric after short-term evaluation; in those patients who were already proteinuric, urinary protein excretion did not increase over time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The Italian Artificial Heart Program.

In Italy, artificial heart development was promoted by virtue of a special program on technological and industrial development in areas related to cardiology and cardiosurgery. A first prototype series of electromechanical total artificial hearts (TAHs) and ventricular assist devices (VADs), with ball-screw-based actuation technology, has been developed, and preliminary bench tests and short-term animal implant experiments were performed. The project started with analysis and development of existing TAH and VAD models, and it included a fill-sensor-free control scheme and anatomical fitting studies using a three-dimensional computer model of the chest cavity. Second-generation prototypes are currently being developed, and they are scheduled for medium-term bench and in vivo testing by early 1994.

Animals↗
PubMed1991

Assisted circulation for myocardial recovery after repair of congenital heart disease.

Between January 1987 and May 1990, six children underwent ventricular assisted circulation for recovery of myocardial function after cardiac surgery. Their ages ranged from 9 months to 12 years. Three patients had tetralogy of Fallot and one had atrioventricular discordance with ventriculoarterial concordance, ventricular septal defect, and under-over ventricles. Double outlet left ventricle and a large ventricular septal defect with pulmonary hypertension was present in the remaining two. The duration of circulatory support averaged 126 +/- 57 h. An extracorporeal membrane oxygenator (ECMO) was used in four patients, biventricular assistance with centrifugal pumps in one, and left ventricular assistance followed by ECMO in the last patient. Circulatory support was begun in the operating room in two patients who could not be weaned from cardiopulmonary bypass. Both these patients are long-term survivors. Assisted circulation was implanted in four patients in the intensive care unit because of low cardiac output refractory to any pharmacological treatment. Only one of these patients could be weaned from circulatory support but he died 20 days later because of multiorgan failure due to persistent poor myocardial function. The causes of death in the remaining three patients were intracranial hemorrhage, untreatable bleeding, and failure of myocardial recovery, respectively. We believe that early postoperative use of circulatory support can be a major determinant for recovery of myocardial function in patients who have severe low cardiac output following repair of congenital cardiac lesions. Our initial experience with the use of biventricular assistance in small children is encouraging. Nevertheless, further observations are clearly necessary to establish the role of postoperative circulatory support in children with congenital cardiac lesions.

Cardiac Output, Low↗
PubMed1991

Nature and extent of glomerular injury induced by cyclosporine in heart transplant patients.

We sought to clarify whether low-dose cyclosporine (5.0 +/- 2.2 mg/kg/day) given for more than two years to prevent cardiac graft rejection induced glomerular injury and to quantify the extent of the lesions. After renal hemodynamic studies, renal biopsy specimens were obtained from 10 patients on cyclosporine and analyzed by a novel morphometric technique consisting of a tridimensional reconstruction of the glomerular tuft. Autopsy kidney specimens from three patients with no clinical history of renal disease, and from four patients who died with dilatative cardiomyopathy served as controls. The glomerular filtration rate and renal plasma flow were significantly depressed below normal values in transplant recipients given cyclosporine, averaging 35 +/- 8 and 325 +/- 94 ml/min/1.73 m2, respectively. Conventional light microscopy of specimens from controls and from patients who died with dilatative cardiomyopathy did not reveal renal structural abnormalities. By contrast kidney specimens from cyclosporine-treated patients had obliterative arteriolopathy and ischemic-type changes, with thickening and wrinkling of glomerular capillary wall. Morphometrical analysis of 28 control glomeruli and 40 glomeruli from patients with dilatative cardiomyopathy showed glomerular capillary tuft volumes (VCT) ranging between 1.2 and 2.3 microns 3 x 10(-6), whereas of 102 glomeruli from cyclosporine-treated patients 42.1% had VCT lower than 1.2 microns 3 x 10(-6) and 24.4% VCT higher than 2.3 microns 3 x 10(-6).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[Circulatory assistance in high-risk coronary angioplasty].

Femoral vein to artery cardiopulmonary by-pass was used during coronary angioplasty in five high risk patients. In four patients the target vessel supplied more than half of the viable myocardium; in one of these, the ejection fraction of the left ventricle was less than 20%. In one patient the relative contraindications for surgery were the patient's age and the presence of concomitant renal failure. Cardiopulmonary support was established by using cut-down cannulae insertion in three patients and by using the percutaneous system in two. In the latter, the support was stand-by, but the abrupt closure of the artery ten minutes after the end of the successful procedure, required the prompt activation of the support and the patient was treated with emergency saphenous graft. The use of the cardiopulmonary support either as a prophylactic or as a stand-by, enabled coronary angioplasty to be performed on these high-risk patients. The clinical and anatomical data relative to the five patients as well as the possible use of the cardiopulmonary support system either as a prophylactic or standby application during high-risk PTCA are discussed.

Adult↗
PubMed1989

Experience with itraconazole in cryptococcosis and aspergillosis.

Cryptococcosis and aspergillosis in immunocompromised patients are extremely difficult clinical conditions to manage and treatment with available antifungal drugs often fails. Itraconazole, R-51211, Janssen Pharmaceutica, a new orally absorbed triazole, is a possible alternative drug which is potentially effective and nontoxic. Preliminary experience with 28 patients, eight with cryptococcosis and 20 with aspergillosis, is reported. Of these patients, 16 were immunocompromised (seven with the acquired immune-deficiency syndrome (AIDS), five heart transplant recipients and four with leukaemia or lymphoma). Overall, results of treatment were good (18 in remission, four markedly improved, four moderately improved and two failed). Prevention of relapses of cryptococcosis was obtained in all patients with AIDS on long-term itraconazole monotherapy (3 mg/kg). Treatment of invasive aspergillosis required a higher dosage (about 5 mg/kg) and prolonged administration. Besides its efficacy this antifungal agent allowed outpatient management.

Acquired Immunodeficiency Syndrome↗
PubMed1989

[Non-invasive diagnosis of acute rejection in heart transplant].

The purpose of this study was to evaluate the sensibility of some clinical and non-invasive parameters in the early diagnosis of cardiac rejection in heart transplant patients. Eighteen patients (15 males and 3 females) aged 13-57 years (mean 44 +/- 14), with orthotopic heart transplant were followed clinically for a mean period of 15 +/- 8.7 months (range 3-27). They were all treated with cyclosporin, associated with azathioprine or prednisone, or both. During the same day of the endomyocardial biopsy, the patients were submitted to a clinical examination, 12 leads ECG and 2-dimensional and Doppler-echocardiography. The following parameters were evaluated: systolic and diastolic blood pressure, heart rate, body weight, summated QRS voltage in the 12 leads ECG, interventricular septum and left ventricular posterior wall end-diastolic thickness, left ventricular myocardial mass and fractional shortening, isovolumic relaxation time. Biopsy specimens were graded according to the Billingham criteria. Totally, 251 biopsies were performed: 130 were negative, 98 positive for mild or moderate rejection, 23 had a resolving rejection pattern; in 61 cases the patients were treated for acute rejection. Compared to negative biopsies, during acute rejection the QRS voltage and the isovolumic relaxation time significantly decreased, while left ventricular wall thickness and body weight increased. To evaluate the effects of the acute immunosuppressive therapy, the same parameters before and after treatment were compared. The QRS voltage, the wall thickness and the isovolumic relaxation time were significantly modified, returning to the pre-rejection values. In conclusion, both clinical and non-invasive information, may be useful to suspect an episode of acute rejection in heart transplant patients and to program myocardial biopsy.

Acute Disease↗