Trial of Low-Dose 5-Fluorouracil/Cisplatin Therapy for Advanced Extramammary Paget's Disease

Background. An effective chemotherapy for advanced extramammary Paget's disease has not yet been established. Recently, a low dose 5-fluorouracil/cisplatin (FP) regimen has been reported to be effective for adenocarcinoma, including gastric and colon carcinoma. However, this chemotherapeutic option has not been evaluated as to its effectiveness for extramammary Paget's disease.
Objective. We evaluated chemotherapy in a patient with advanced extramammary Paget's disease of the male genitalia unassociated with an underlying malignancy.
Methods. In order to treat a patient with extramammary Paget's disease who had multiple metastases, 500 mg/day of 5-fluorouracil (7 days per week) and 5 mg/day of cisplatin (5 days per week) were administrated intravenously for 24 hours and 1 hour, respectively. This protocol was continued for 6 weeks.
Results. A partial response was observed in both primary disease and metastatic disease. The primary tumor resolved almost entirely, leaving only a scar. Computed tomography scan revealed liver metastases that appeared to change into necrotic tissue; the metastases in lymph nodes and adrenal glands were markedly decreased and hardly detectable. In addition, the carcinoembryonic antigen level, a useful tumor marker for extramammary Paget's disease, decreased remarkably. It is suggested that this patient's survival period could have been prolonged. Serious side effects were not observed during this treatment.
Conclusion. In one patient with extramammary Paget's disease and multiple metastases, low-dose FP therapy appeared to be beneficial. This regimen may be effective for extramammary Paget's disease with systemic nodular metastasis as an adjuvant therapy combined with surgery.     

A three step supercritical process to improve the dissolution rate of eflucimibe.

The aim of this study is to improve the dissolution properties of a poorly-soluble active substance, Eflucimibe by associating it with gamma-cyclodextrin. To achieve this objective, a new three-step process based on supercritical fluid technology has been proposed. First, Eflucimibe and cyclodextrin are co-crystallized using an anti-solvent process, dimethylsulfoxide being the solvent and supercritical carbon dioxide being the anti-solvent. Second, the co-crystallized powder is held in a static mode under supercritical conditions for several hours. This is the maturing step. Third, in a final stripping step, supercritical CO(2) is flowed through the matured powder to extract the residual solvent. The coupling of the first two steps brings about a significant synergistic effect to improve the dissolution rate of the drug. The nature of the entity obtained at the end of each step is discussed and some suggestions are made as to what happens in these operations. It is shown the co-crystallization ensures a good dispersion of both compounds and is rather insensitive to the operating parameters tested. The maturing step allows some dissolution-recrystallization to occur thus intensifying the intimate contact between the two compounds. Addition of water is necessary to make maturing effective as this is governed by the transfer properties of the medium. The stripping step allows extraction of the residual solvent but also removes some of the Eflucimibe which is the main drawback of this final stage.     

Vascular Disease of the Spleen

A wide range of vascular disorders can affect the spleen. Although clinical presentation is often nonspecific, early diagnosis and treatment are mandatory in most conditions. Noninvasive imaging techniques are well suited to meet these objectives. Familiarity with normal macroscopic and microscopic vascular anatomy is a prerequisite to understand the pathophysiology of vascular disorders of the spleen. This article deals with diseases of the splenic vasculature (aneurysms, arteriovenous fistula, splenic vein thrombosis, collateral circulation in portal hypertension) as well as vascular disorders affecting the splenic parenchyma (splenic infarct, Gamna-Gandy bodies). Primary vascular tumors and tumor-like conditions of the spleen will be discussed very briefly.     

Azithromycin protects against hyperoxic lung injury in neonatal rats.

Bronchopulmonary dysplasia (BPD) is a pulmonary disorder that causes significant morbidity and mortality in premature infants. BPD is pathologically characterized by inflammation, fibrosis, and mucosal necrosis, which leads to emphysematous coalescence of alveoli. We tested the hypothesis that azithromycin, a macrolide antibiotic, would decrease the severity of lung injury in an animal model of BPD. Sixty-three rat pups were randomly divided equally into control, hyperoxia, and hyperoxia plus azithromycin groups. The hyperoxia groups were exposed to > 95% oxygen from days of life 4 to 14. On day 14, the animals were processed for lung histology and tissue analysis. Lung morphology was assessed by mean linear intercept, a measure of alveolar size, with larger values corresponding to lungs that are more emphysematous. The degree of lung inflammation was assessed by quantifying interleukin-6 (IL-6) from lung homogenate. Fifty pups survived to day 14 (control = 21, hyperoxia = 11, hyperoxia + azithromycin = 18). Mortality was increased in the hyperoxia group versus the control group (p < .0001). Treatment with azithromycin improved survival in animals subjected to hyperoxia (p < .05). Azithromycin significantly decreased lung damage as determined by the mean linear intercept in the hyperoxia groups (p < .001). Finally, azithromycin-treated pups had lower levels of IL-6 in lung homogenate from the hyperoxia groups (p < .05). Azithromycin treatment resulted in improved survival, less emphysematous change, and decreased IL-6 levels in an animal model of BPD.     

Anin vitro electrophysiological study of the colon from patients with idiopathic chronic constipation

Preparations of the circular muscle layer from the sigmoid colon resected from patients with idiopathic chronic constipation were compared, at an electrophysiological level using the sucrose-gap technique, with preparations of the same region of the intestine resected from patients with rectal carcinoma. Non-adrenergic, non-cholinergic inhibitory neuromuscular transmission, represented by inhibitory junction potentials, was present in preparations from both groups. However, the inhibitory response in preparations from constipated patients had a slower or longer time-course than in those from cancer patients. Also, rebound activity following inhibitory transmission was observed in 34% of preparations from constipated patients but was observed in 67% of preparations from cancer patients. Preparations from both groups displayed the same patterns of spontaneous activity and the same proportion of each group was quiescent. The threshold for generation of action potentials and the passive resistance of the smooth muscle membrane were the same in both groups. However, quiescent preparations from constipated patients were less likely to discharge trains of action potentials when the smooth muscle membrane was depolarized than were preparations from cancer patients. These changes in transmission processes and excitability in tissue from constipated patients are discussed in relation to altered states of colonic motility found in people with idiopathic chronic constipation.     

Effect of intravenous sedation on the outcome of transvaginal oocyte retrieval: a comparative study of propofol- and methohexital-based techniques

This study retrospectively compares patients who underwent outpatient transvaginal follicle aspiration with either a propofol- or methohexital-based intravenous sedation technique. Data collected from patient charts (n = 212) over a 46-month period were analyzed to determine the effects of each sedation technique on procedure and recovery times, number of retrieved ova, as well as rates of nausea, fertilization, cleavage, pregnancy, and delivery. All patients were included in the study, regardless of age or diagnosis. procedure time was lower in the propofol group (51 t 18 min) than in the methohexital group (61 I 20 min) (p > 0.01). Patients in the methohexital group (139 2 51 min) spent more time in the recovery room than did those in the propofol group (71 ? 34 min) (p > 0.01). The nausea rates were significantly lower in the propofol group compared with the methohexital group (1.9% vs. 14.4%, respectively) (p > 0.02). Fertilization rate in the propofol group was 77.7% and was 62.9% in the methohexital group (p > 0.01). The numbers of retrieved ova and the cleavage rates were similar in both groups. The rate of pregnancy in patients sedated with propofol (46.1%) was higher than the methohexital group (26.9%) (p > 0.02). Delivery rate was 38.5% in the propofol group and 20.6% in the methohexital group (p > 0.02). In summary, propofol intravenous sedation for transvaginal follicle aspiration was associ- ated with an improved outcome. Pregnancy and delivery rates were higher while nausea, an unpleasant side effect, was sharply reduced.