Use of dexamethasone with mesna for the prevention of ifosfamide-induced hemorrhagic cystitis

AIM: Hemorrhagic cystitis (HC) is a limiting side-effect of chemotherapy with ifosfamide (IFS). In the study presented here, we investigated the use of dexamethasone in combination with mesna for the prevention of IFS-induced HC. METHODS: Male Wistar rats (150-200 g; 6 rats per group) were treated with saline or mesna 5 min (i.p.) before and 2 and 6 h after (v.o.) administration of IFS. One, two or three doses of mesna were replaced with dexamethasone alone or with dexamethasone plus mesna. Cystitis was evaluated 24 h after its induction by the changes in bladder wet weight and by macroscopic and microscopic analysis. RESULTS: The replacement of the last dose or the last two doses of mesna with dexamethasone reduced the increase in bladder wet weight induced by IFS by 84.79% and 89.13%, respectively. In addition, it almost abolished the macroscopic and microscopic alterations induced by IFS. Moreover, the addition of dexamethasone to the last two doses of mesna was more efficient than three doses of mesna alone when evaluated microscopically. CONCLUSION: Dexamethasone in combination with mesna was efficient in blocking IFS-induced HC. However, the replacement of last two doses of mesna with saline or all of the mesna doses with dexamethasone did not prevent HC.     

Hemodynamic Comparison by Doppler Echocardiography of Valves in the Aortic Position

In 281 patients, we used Doppler echocardiography to compare the hemodynamic performance of different aortic prosthetic valves at three postoperative stages and investigated the value of the continuity equation in diagnosing aortic prosthetic obstruction. A baseline study was performed in 163 patients, a 5 ± 2-month follow-up study was performed in 103 patients, and a 15 ± 5-month follow-up study was performed in 65 patients. From baseline to the second study, left ventricular diastolic diameter, heart rate, and maximum (MG) and mean Doppler-derived gradient (MeG) decreased significantly, and left ventricular shortening fraction, systolic blood pressure, stroke volume, and prosthetic valvular area (PVA) increased significantly. No changes were found between the second and third studies. Thus, noninvasive hemodynamic values at the time of follow-up are reported in 171 patients: 86 with Björk-Shiley Monostrut, 27 with Carbomedics, 11 with Medtronic-Hall, 18 with Hancock modified, and 29 with Toronto valve bioprosthesis. Patients implanted with the Toronto had a larger prosthetic size (Monostrut 23 ± 2 mm, Carbomedics 23 ± 3 mm, Medtronic-Hall 23 ± 2 mm, Hancock 23 ± 2 mm, Toronto 25 ± 2 mm, P < 0.01) despite a similar body surface area. MeG and MG were lower (MeG [in mmHg] Monostrut 12 ± 5, Carbomedics 14 ± 6, Medtronic-Hall 19 ± 6, Hancock 11 ± 4, Toronto 7 ± 5; P < 0.01 between Toronto and all others), and PVA was greater (Monostrut 2.0 ± 0.7 cm², Carbomedics 1.8 ± 0.8 cm², Medtronic-Hall 1.6 ± 0.7 cm², Hancock 1.7 ± 0.5 cm², Toronto 2.2 ± 0.9 cm²; P < 0.01 between Toronto and Carbomedics, Medtronic-Hall, and Hancock), even compared with the same sizes in the other valves. A PVA of 0.9 cm² or less and MeG of 28 mmHg or more identified prosthetic obstruction with 100% sensitivity and 99% specificity. Hemodynamics change significantly from the early to the late postoperative state. The Toronto valve stentless porcine bioprostheses performs hemodynamically better than other valves. PVA measurement using the continuity equation may accurately identify prosthetic obstruction.     

The Ross Operation: The Autologous Pulmonary Valve in the Aortic Position

Aortic valve replacement (AVR) with a pulmonary valve autograft (PVA) was first reported by Donald N. Ross (DNR) in 1967. The expectation of this procedure was to avoid degenerative changes seen in other biological tissue valves such as calcification, attenuation, and rupture of the leaflets. Recent reports by the original investigator's group have confirmed the lack of degenerative changes in PVA. To corroborate their conclusions, the fate of 12 patients undergoing AVR with PVA by one of us (LGL) has been ascertained. From March 1969 to June 1971, 12 patients underwent AVR with PVA. The right ventricular outflow tract (RVOT) was reconstructed with an aortic homograft valved conduit. The mean age was 42.7 years (range 21 to 52 years). The mean follow-up for 11 hospital survivors is 12.4 years. Three PVA have been replaced; one following infective endocarditis at 13 years, and two at 15 and 73 months due to technical malalignment. There was no evidence of PVA degeneration during histological examination of these explanted PVAs. Six patients are alive and retain the original PVA at 12 years (55%). This analysis corroborates the conclusions of the DNR report and strongly suggests an immunological mechanism in the process of calcification of other biological tissue valves. The Ross operation is advocated for AVR in young patients as valve durability is of paramount importance especially in this group.     

Pulmonary Venous Flow and Correlates in Patients with Aortic Stenosis

In order to determine the value of pulmonary venous flow (PVF) pulsed Doppler measurements in assessing filling pressures in aortic stenosis (AS), we studied 20 patients by transthoracic and transesophageal echocardiography and catheter examination. Peak systolic PVF correlated with pulmonary capillary wedge pressure (PCWP) (r =-0.67, P < 0.01), the ratio of peak systolic to diastolic PVF correlated with PCWP (r =-0.68, P < 0.01) and left ventricular end-diastolic pressure (r =-0.51, P < 0.01). Peak systolic PVF < 40 cm / sec was highly sensitive and specific in the detection of PCWP ≥ 15 mmHg (100% and 84%, respectively). Correlations between PVF and pulsed Doppler transmitral indices were also found (r = 0.66 between peak systolic to diastolic PVF and peak late transmitral velocity, P < 0.01); however, PVF indices predicted filling pressures better than Doppler transmitral indices. In conclusion PVF indices are accurate predictors of high filling pressures in AS patients.     

Synthesis of aldehydic peptides inhibiting renin

Reduction of peptidyl N,O-dimethyl hydroxamates with lithium aluminium hydride in diethyl ether at 0° allowed the preparation of peptidyl aldehydes in excellent yield and optical purity. These aldehydic peptides are able to inhibit renin activity. They are the shortest renin inhibitors known to date.     

Bullous pemphigoid induced by Frusemide

A patient who developed bullous lesions of pemphigoid type, confirmed immunopathologically, is reported in whom the most likely cause was Frusemide. This appears to be the third reported case of this type of bullous drug eruption.     

Repetitive BOP coupling (REBOP) in solid phase peptide synthesis

The coupling reagent (benzotriazol-1-yloxy)tris-(dimethylamino)phosphonium (BOP) hexafluorophosphate was tested in the synthesis of luliberin (LH-RH) with inexpensive classically protected Boc-amino acids, in slight excess, and benzhydryl amino resin, without any other additive. The good solubility of this reagent and its by-products is of particular interest for automated peptide synthesis. [D-H-S¹]LH-RH was also synthesized and compared with LH-RH by proton nuclear magnetic resonance spectroscopy. As shown by the biological tests and the high performance liquid chromatography study, unprotected pyroClu and Boc-His can be used without any significant racemization but Boc-His(Boc) was found to be preferable since it gave no detectable racemization and no by-products. The difficult isolation of the minority D-derivative from the crude preparation of LH-RH was resolved by a recycling procedure in reversed phase HPLC.