Cleft palate and ventilation tubes: a prophylactic dilemma.

OBJECTIVE: This study aimed to understand, in a long-term follow-up study, whether the placement of grommets had been necessary after cleft palate surgical correction. METHOD: A case-control, retrospective study was carried out on consecutive paediatric patients who underwent surgical repair of a cleft palate. RESULTS: The study population included 138 patients, divided into 2 groups: group 1 - patients in whom grommets were placed at the time of cleft palate surgery, and group 2 - patients in whom grommets were not placed at the time of cleft palate surgery. During the follow up, in groups 1 and 2, 65.2 per cent and 67.8 per cent, respectively, did not need subsequent grommet placement after cleft palate surgery. CONCLUSION: Of patients, 56.5 per cent did not need ventilation tubes at any point during follow up. The placement of grommets is not innocuous; therefore, its use at the time of cleft palate surgical repair should be reconsidered.

Amifostine and glutathione prevent ifosfamide- and acrolein-induced hemorrhagic cystitis.

INTRODUCTION: Ifosfamide (IFS) is an antineoplastic alkylating agent whose major side effect is hemorrhagic cystitis (HC). This toxicity is attributed to the renal excretion of acrolein (ACR), a highly urotoxic IFS metabolite. Despite the clinical use of mesna to prevent HC, a significant percent ( approximately 33%) of patients present with at last one feature of HC, mainly hematuria. AIM: To investigate the use of two antioxidants-amifostine and glutathione-for the prevention of experimental IFS- and ACR-induced HC. MATERIALS AND METHODS: Male Swiss mice were treated intraperitoneal (i.p.) with saline (control), glutathione (125, 250 or 500 mg/kg) or amifostine (25, 50 or 100 mg/kg), and 30 min later they received a single i.p. injection of IFS at a dose of 400 mg/kg. To investigate the systemic effects of the antioxidants on ACR-induced HC, the animals were treated with saline, amifostine (50 mg/kg, i.p.) or glutathione (500 mg/kg, i.p.), and 30 min afterward with 75 mug ACR intravesically (i.ve.). In another set of experiments, the antioxidants were injected directly into the bladder, where the mice received a single i.ve injection of ACR (75 mug) plus amifostine (1.5 mg/kg) or glutathione (2 mg/kg). HC was measured 3 h after IFS or ACR injection according to bladder wet weight, macroscopic (edema and hemorrhage) and microscopic changes, i.e., edema, hemorrhage, cellular infiltration, fibrin deposition and urothelial desquamation. RESULTS: Pretreatments with amifostine or glutathione prevented IFS-induced HC in a dose-dependent manner. Furthermore, ACR-induced HC was also prevented by systemic (i.p.) or local (i.ve.) pretreatment with glutathione or amifostine. The greatest protective effect was seen with local amifostine treatment (2 mg/kg i.ve.) (P < 0.05). CONCLUSIONS: Glutathione and amifostine show a beneficial effect in experimental IFS- and ACR-induced HC. Thus, they should be investigated as an alternative treatment to prevent HC observed in patients undergoing IFS treatment.

A model of hemorrhagic cystitis induced with acrolein in mice.

Acrolein is a urinary metabolite of cyclophosphamide and ifosfamide, which has been reported to be the causative agent of hemorrhagic cystitis induced by these compounds. A direct cytotoxic effect of acrolein, however, has not yet been demonstrated. In the present study, the effects of intravesical injection of acrolein and mesna, the classical acrolein chemical inhibitor, were evaluated. Male Swiss mice weighing 25 to 35 g (N = 6 per group) received saline or acrolein (25, 75, 225 microg) intravesically 3, 6, 12, and 24 h before sacrifice for evaluation of bladder wet weight, macroscopic and histopathological changes by Gray's criteria, and 3 and 24 h for assessment of increase in vascular permeability. In other animals, mesna was administered intravesically (2 mg) or systemically (80 mg/kg) 1 h before acrolein. Intravesical administration of acrolein induced a dose- and time-dependent increase in vascular permeability and bladder wet weight (within 3 h: 2.2- and 21-fold increases in bladder wet weight and Evans blue dye exuded, respectively, at doses of 75 microg/bladder), as confirmed by Gray's criteria. Pretreatment with mesna (2-mercaptoethanesulfonic acid), which interacts with acrolein resulting in an inactive compound, inhibited all changes induced by acrolein. Our results are the first demonstration that intravesical administration of acrolein induces hemorrhagic cystitis. This model of acrolein-induced hemorrhagic cystitis in mice may be an important tool for the evaluation of the mechanism by which acrolein induces bladder lesion, as well as for investigation of new uroprotective drugs.

A model of hemorrhagic cystitis induced with acrolein in mice

Acrolein is a urinary metabolite of cyclophosphamide and ifosfamide, which has been reported to be the causative agent of hemorrhagic cystitis induced by these compounds. A direct cytotoxic effect of acrolein, however, has not yet been demonstrated. In the present study, the effects of intravesical injection of acrolein and mesna, the classical acrolein chemical inhibitor, were evaluated. Male Swiss mice weighing 25 to 35 g (N = 6 per group) received saline or acrolein (25, 75, 225 æg) intravesically 3, 6, 12, and 24 h before sacrifice for evaluation of bladder wet weight, macroscopic and histopathological changes by Gray's criteria, and 3 and 24 h for assessment of increase in vascular permeability. In other animals, mesna was administered intravesically (2 mg) or systemically (80 mg/kg) 1 h before acrolein. Intravesical administration of acrolein induced a dose- and time-dependent increase in vascular permeability and bladder wet weight (within 3 h: 2.2- and 21-fold increases in bladder wet weight and Evans blue dye exuded, respectively, at doses of 75 æg/bladder), as confirmed by Gray's criteria. Pretreatment with mesna (2-mercaptoethanesulfonic acid), which interacts with acrolein resulting in an inactive compound, inhibited all changes induced by acrolein. Our results are the first demonstration that intravesical administration of acrolein induces hemorrhagic cystitis. This model of acrolein-induced hemorrhagic cystitis in mice may be an important tool for the evaluation of the mechanism by which acrolein induces bladder lesion, as well as for investigation of new uroprotective drugs.

Effects of the tumour necrosis factor-alpha inhibitors pentoxifylline and thalidomide in short-term experimental oral mucositis in hamsters.

Oral mucositis is a frequent side-effect of cancer therapy. A definitive method of prophylaxis or treatment is not yet available. As pentoxifylline (PTX) and thalidomide (TLD) have been shown to inhibit cytokine synthesis, we studied the effects of these cytokine inhibitors in an experimental oral mucositis model. Oral mucositis was induced in Golden hamsters by the administration of 5-fluorouracil (5-FU) followed by mechanical trauma of the cheek pouch. On days 4, 5, 10, 12, 14 and 16, lesions induced by 5-FU were examined macroscopically and microscopically, and the presence and intensity of hyperemia, erythema, edema, inflammatory cell infiltration, hemorrhagic areas, ulcers and abscesses were recorded. Saline (control), PTX (5, 15, 45 mg kg(-1)) or TLD (10, 30, 90 mg kg(-1)) were administered daily and animals were killed on day 10 for macroscopic and histological analysis and assay of myeloperoxidase (MPO) activity. Animals were weighed daily, and total and differential leukocyte counts were performed on peripheral blood. PTX and TLD were found to reduce the macroscopic and histological parameters of oral mucositis and MPO activity. PTX and TLD also reversed peripheral neutrophilia, but only PTX prevented weight loss. The results indicate a protective effect of PTX and TLD, suggesting an important role for tumour necrosis factor-alpha (TNF-alpha) in the pathophysiology of 5-FU induced-oral mucositis in hamsters.

[Prepubertal testicular tumors]. / Tumores testiculares na pré-puberdade.

Prepubertal testis tumours (T.T) are rare, with different characteristics and clinical course to adults and with a better prognosis. The authors report the experience of Maria Pia Hospital's over a 15 year period. There were 8 cases of T.T.: 3 Yolk sac tumours, 3 teratomas, 1 Leydig cell tumour and 1 epidermoide cyst. All patients are submitted to an inguinal orchiectomy. Follow-up ranged between six months and 14 years. There was no recurrence of the disease in seven patients are without disease recurrence. Mortality was nil.

Acute gastric volvulus and congenital posterolateral diaphragmatic hernia.

Acute gastric volvulus in infancy is a rare disorder and a surgical emergency. Prompt clinical suspicion and radiological assessment are essential for this life-threatening condition. We report a 3-month-old female case, admitted for an initial suspicion of an intestinal obstruction. She presented unproductive retching, respiratory distress, epigastric distension and lethargy. It was not possible to introduce a naso-gastric tube. A radiological contrast study showed an occluded cardio-esophageal junction without passage of barium, two gastric fluid levels and a horizontally positioned stomach occupying the inferior portion of the left hemithorax, suggesting a left diaphragmatic hernia. Laparotomy revealed an acute mesenterico-axial gastric volvulus with a left posterolateral diaphragmatic hernia. The stomach volvulus was untwisted, the diaphragmatic defect was repaired after reduction of the herniated contents and no gastropexy was done. At 3 and 6-months follow-up examination the infant was asymptomatic and thriving.