Intrathecal gadolinium (gadopentetate dimeglumine) enhanced magnetic resonance myelography and cisternography: results of a multicenter study

RATIONALE AND OBJECTIVES: This cooperative multicenter human study was designed to evaluate the safety, magnetic resonance (MR) imaging characteristics, and clinical response to a single gadolinium contrast agent: gadopentetate dimeglumine. MATERIAL AND METHODS: Ninety-five patients (age range: 1 month to 78 years; sex: 50 males, 45 females) were included in this prospective study. The patients presented clinically with a variety of cranial or spinal signs and symptoms for which an intrathecal contrast myelogram or cisternogram was requested by clinical staff. Via lumbar puncture (20-25 g needle), 3 to 5 mL/ml of cerebrospinal fluid were withdrawn and mixed with a single volume of 0.5 (n = 63), 0.7 (n = 13), 0.8 (n = 12), or 1.0 (n = 7) cc/mL of gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany). This was then injected into the subarachnoid space, and the needle was removed. Immediate and delayed (up to 96 hours) T1- and T2-weighted MR imaging was performed on super conductive, high-field (1.0-1.5 tesla) imaging units in two or three planes. All patients were hospitalized for an observation period of 24 hours following the procedure, and follow-up neurologic examinations were performed serially for 6 to 12 months afterward. RESULTS: No patient manifested gross behavioral changes, neurologic alterations, or seizure activity at any time following the procedure. Nineteen patients (20%) experienced postural postlumbar puncture headache, six patients had nausea (6%), and two patients had episodes of vomiting (2%), all which resolved within the first 24 hours of the lumbar puncture with conservative bed rest. CONCLUSION: This cooperative study demonstrates the general safety and feasibility of low dose (0.5-1.0 mL/ml) intrathecal gadopentetate dimeglumine administration. The potential useful clinical applications include the evaluation of obstructions and communications of the various subarachnoid spaces, spontaneous or traumatic/postsurgical craniospinal cerebrospinal fluid leaks, and subarachnoid space CSF flow and parenchymal CNS interstitial diffusion dynamics. This worldwide cooperative study seeks to progressively perform human studies for further definitive evaluation of the practical clinical applications, of the relationship of this technique to other imaging studies and modalities, and the long-term safety of the procedure in a larger number of subjects.     

Neoadjuvant chemotherapy with taxotere-epirubicin-5-fluorouracil (TEF) in local-regionally advanced breast cancer: a preliminary report

AIMS AND BACKGROUND: Sixty-three patients with local-regionally advanced breast cancer were treated with neoadjuvant chemotherapy consisting of docetaxel (Taxotere), epirubicin, and 5-fluorouracil (TEF). METHODS AND STUDY DESIGN: Preoperatively, patients received four cycles of Taxotere (80 mg/m2), epirubicin (60 mg/m2), and 5-fluorouracil (500 mg/m2), repeated every 21 days. Following completion of four cycles of chemotherapy, appropriate surgery was performed. After the surgery, patients received one cycle of the TEF chemotherapy regimen; following chemotherapy, radiotherapy was applied, and at the end two more cycles of TEF chemotherapy regimen were given. RESULTS: Sixty-three patients with locally advanced breast cancer were treated. Three patients were excluded from the study before the evaluation of response. Median age of the patients was 50 years (range, 25-77). Twenty-seven and 33 patients were premenopausal and postmenopausal, respectively. Thirty-nine patients were in stage IIIA and 21 in stage IIIB. Complete and partial responses were observed in 15 (25%) and 42 (70%) of the patients following four cycles of preoperative TEF chemotherapy regimen, respectively. Overall response was 95%, and primary lesion progressed only in 3 (5%) patients. The mean disease-free survival was 15.9 +/- 6.8 (range, 3.5-28) months and the mean overall survival was 18.6 +/- 7.2 (range, 5-30) months. The most frequent side effects were nausea-vomiting, mucositis, alopecia and leukopenia. CONCLUSIONS: TEF therapy is a treatment with a high overall response rate and toxicities similar to other taxotere combinations. A longer follow-up of patients is necessary for the determination of disease-free survival and overall survival.     

Determination of apoptosis through Bax expression in cryptorchid testis: an experimental study

The aim was to determine the expression of Bax in germ cells of rats with unilateral experimental cryptorchidism, and to evaluate the role of apoptosis in germ cell loss. Twenty-one prepubertal rats were randomly subdivided into three groups after the execution of the left cryptorchidism model. Group 1 (n=8), group 2 (n=6) and group 3 (n=7) rats were killed at the end of the first, second and third month, respectively. Bax expression was assessed in Sertoli cells, spermatogonia and spermatocytes by immunohistochemistry. Percentages of Bax expression in spermatocytes and spermatogonia were decreased in the left testicles in the 2^nd and 3^rd months compared to results obtained in the 1^st month (p<0.05). Percentage of Bax expression in the left testicles of group 1, at the level of both spermatogonia and spermatocytes was higher than that in the right one (p<0.05). However, in groups 2 and 3, the higher Bax expression on the left side was only seen in the spermatocytes (p<0.05). In all groups, the mean weight of the left testicle was lower than that of the scrotal counterpart where the difference was significant only in groups 1 and 3 (p<0.05). The weight of the left and right testicles was increasing with time. In this model of cryptorchidism, the affected testis had a decreased weight compared to the normal one. Based on the increased Bax expression, we think that apoptosis may play a role in the germ cell loss.     

Efficacy of COX-2 inhibitors in a case of congenital nephrogenic diabetes insipidus

A 17-month-old boy presented with failure to thrive, polyuria, and vomiting. He had been diagnosed clinically with nephrogenic diabetes insipidus and treated by amiloride and hydrochlorothiazide combination without a satisfactory outcome at another center since 1 year of age. The diagnosis was confirmed by genetic analysis (AVPR2mutation), and the treatment was modified to include rofecoxib (a selective cyclooxygenase-2 inhibitor) in addition to hydrochlorothiazide and amiloride. This combination along with a low-salt diet resulted in a dramatic decrease in urinary free-water loss, while no side effect was noted. Because of prohibition of rofecoxib, it had to be substituted first by indomethacin and then by ibuprofen. However, both drugs were ineffective in controlling water diuresis. Thus, we had to replace these drugs by celecoxib (another selective cyclooxygenase-2 inhibitor). We conclude that the combination hydrochlorothiazide/amiloride/cyclooxygenase-2 inhibitor could be successfully used to treat congenital nephrogenic diabetes insipidus.     

The plateled-derived growth factor level (PDGF) in Hodgkin's disease and non-Hodgkin's lymphoma and its relationship disease activation

The research reported in this paper was designed to study the role of plateled-derived growth factor (PDGF) in Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHL). The PDGF levels in 9 patients with HD and 12 NHL and in a control group consisting of 20 people, was measured by ELISA method. The PDGF values in the disease group of 19 patients were raised. The values of PDGF in the control group were 28.977+/-9 pg/ml, but were measured at 147.083+/-54 pg/ml in HD group and 131.487+/-56 pg/ml in NHL group (p < 0.01). The observation of a 5-fold increase in PDGF values in the disease group when compared to the control group suggests that PDGF could itself be considered as a possible factor in the pathogenesis of HD and NHL. In order to support this, there is a need to design additional studies monitoring PDGF in larger number of patients at various stages of the disease.     

A 24-week randomized, double-blind, placebo-controlled study of escitalopram for the prevention of generalized social anxiety disorder

OBJECTIVE: Escitalopram has proven efficacy in the short-term treatment of generalized social anxiety disorder (SAD). The present relapse prevention study investigated relapse rates during a 24-week, randomized, double-blind, placebo-controlled period in patients with generalized SAD who had responded to 12-week open-label treatment with escitalopram. METHOD: A total of 517 patients with a primary diagnosis of generalized SAD (per DSM-IV criteria) and a Liebowitz Social Anxiety Scale (LSAS) total score of > or = 70 received 12 weeks of open-label treatment with flexible doses (10-20 mg/day) of escitalopram. Of these patients, 371 responded (Clinical Global Impressions-Improvement scale [CGI-I] score of 1 or 2) and were randomly assigned to 24 weeks of double-blind treatment with escitalo-pram (10 or 20 mg/day) (N = 190) or placebo (N = 181), continuing with the dose level administered at the end of the open-label period. Relapse was defined as either an increase in LSAS total score of > or = 10 or withdrawal due to lack of efficacy, as judged by the investigator. The study was conducted from January 2001 to June 2002. RESULTS: Survival analysis of relapse and time to relapse showed a significant advantage for escitalopram compared to placebo (log-rank test: p < .001). The risk of relapse was 2.8 times higher for placebo-treated patients than for escitalopram-treated patients (p < .001), resulting in significantly fewer escitalopram-treated patients relapsing (22% vs. 50%), at both doses. Escitalopram was well tolerated during double-blind treatment of generalized SAD, and only 2.6% of the escitalopram-treated patients withdrew because of adverse events. The overall discontinuation rate, excluding relapses, was 13.2% for patients treated with escitalopram and 8.3% for patients treated with placebo. CONCLUSION: Escitalopram was effective and well tolerated in the long-term treatment of generalized SAD.