Modafinil augmentation of selective serotonin reuptake inhibitor therapy in MDD partial responders with persistent fatigue and sleepiness.

BACKGROUND: Partial response, no response, or residual symptoms following antidepressant therapy is common in clinical psychiatry. This study evaluated modafinil in patients with major depressive disorder (MDD) who were partial responders to adequate selective serotonin reuptake inhibitor (SSRI) therapy and excessive sleepiness and fatigue. METHODS: This retrospective analysis pooled the data of patients (18-65 yrs) who participated in two randomized, double-blind, placebo-controlled studies of modafinil (6-week, flexible-dose study of 100-400 mg/day or 8-week, fixed-dose study of 200 mg/day) plus SSRI therapy. Patients (n=348) met criteria for several residual symptoms (Epworth Sleepiness Scale [ESS] score>or=10; 17-item Hamilton Depression Scale [HAM-D] score between 4 and 25; and Fatigue Severity Scale [FSS] score>or=4). RESULTS: Compared to placebo, modafinil augmentation rapidly (within 1 week) and significantly improved overall clinical condition (Clinical Global Impression-Improvement), wakefulness (ESS), depressive symptoms (17-item HAM-D), and fatigue (FSS) (p<.01 for all). At final visit, patients receiving modafinil augmentation experienced statistically significant improvements in overall clinical condition, wakefulness, and depressive symptoms. Modafinil was well tolerated in combination with SSRI. CONCLUSIONS: Results of this pooled analysis provide further evidence suggesting that modafinil is an effective and well-tolerated augmentation therapy for partial responders to SSRI therapy, particularly when patients continue to experience fatigue and excessive sleepiness.     

A multicenter clinical trial of gadolite oral suspension as a contrast agent for MRI

The purpose of this study was to assess the effectiveness and safety of Gadolite Oral Suspension as a gastrointestinal (GI) contrast agent for MRI in a phase II and two phase III multicenter clinical trials. Gadolite was administered to 306 patients with known or suspected abdominal and/or pelvic disease. MRI with T1- and T2-weighted sequences was performed before and after ingestion. Efficacy was evaluated by having two masked readers rate the certainty of their MR diagnosis (0 = uncertain, 1 = probable, 2 = definite) on randomly presented pre- and post-Gadolite Oral Suspension enhanced images. Principal investigators also evaluated the images and established the final diagnosis. Vital signs, clinical chemistries, and adverse events were documented. Blood and urine samples were analyzed for gadolinium content to determine whether Gadolite Oral Suspension was absorbed systemically. Certainty in MR diagnosis increased significantly (P < .001) for both blinded readers between pre- and post-Gadolite images (.49–1.18 for reader 1; .46–1.53 for reader 2). Sensitivity, specificity, and accuracy also increased for both masked readers. No gadolinium was detected in blood or urine samples. There were no serious adverse events and no apparent drug-related trends in mean vital signs or laboratory values. Gadolite is a highly effective, safe, and well tolerated contrast agent for clinical use with MRI.     

Cervical Cancer with Paraaortic Metastases: Significance of Residual Paraaortic Disease after Surgical Staging

Cervical carcinoma frequently metastasizes to the paraaortic region, necessitating extended field radiotherapy to effect a cure. As imaging modalities are unreliable in identifying all cases of paraaortic nodal metastases (PAN), surgical staging is often utilized prior to radiotherapy. This study was aimed at identifying factors predictive of survival in women with cervical carcinoma and paraaortic metastases. In particular, survival based on extent of paraaortic disease was examined. The study group consisted of 43 women (stages IB–IVB) identified between 1982 and 1993 who were treated with extended field radiation for cervical carcinoma with histologically confirmed paraaortic metastases. The estimated 5-year survival for the study population was 24% with a median survival of 18 months. Pelvic tumor size had a significant impact on survival with the median survival being 34 months if the primary lesion was <6 cm compared to 14 months if ≥6 cm (P= 0.01). Eight of the 26 (31%) women without residual PAN disease after surgical staging remain alive and disease free (mean follow-up, 74 months). In contrast, only 1 of the 17 (6%) women with gross residual PAN is alive 71 months after treatment (P= 0.05). However, a comparison of Kaplan–Meier survival curves did not show a statistically significant advantage to the surgical excision of grossly involved PAN (P= 0.98). Although long-term survival among women with grossly involved, unresected paraaortic metastases is uncommon, further study is necessary to elucidate the role of surgical excision of bulky aortic disease in women with cervical cancer.     

Leukemoid reaction: a diagnostic clue in metastatic carcinoma mimicking classic Hodgkin lymphoma

We report on 2 patients who were initially suspected to have classic Hodgkin lymphoma because of lymphadenopathy and the presence of Reed-Sternberg-like cells. Both patients had an associated leukemoid reaction (using a threshold leukocyte count of 50 000/microL) and were eventually diagnosed with metastatic carcinoma. Disseminated carcinoma can mimic Hodgkin lymphoma clinically, radiologically, and histologically. Reed-Sternberg-like cells may be found in carcinomas, and they represent a particularly challenging diagnostic pitfall for the unwary. When these cells lead to a suspicion of Hodgkin lymphoma, the presence of a leukemoid reaction should prompt the pathologist to question the diagnosis. Misdiagnosis can be avoided by the use of cytokeratin whenever a leukemoid reaction is present in a suspected case of Hodgkin lymphoma.     

Optimal field splitting for large intensity-modulated fields

The multileaf travel range limitations on some linear accelerators require the splitting of a large intensity-modulated field into two or more adjacent abutting intensity-modulated subfields. The abutting subfields are then delivered as separate treatment fields. This workaround not only increases the treatment delivery time but it also increases the total monitor units (MU) delivered to the patient for a given prescribed dose. It is imperative that the cumulative intensity map of the subfields is exactly the same as the intensity map of the large field generated by the dose optimization algorithm, while satisfying hardware constraints of the delivery system. In this work, we describe field splitting algorithms that split a large intensity-modulated field into two or more intensity-modulated subfields with and without feathering, with optimal MU efficiency while satisfying the hardware constraints. Compared to a field splitting technique (without feathering) used in a commercial planning system, our field splitting algorithm (without feathering) shows a decrease in total MU of up to 26% on clinical cases and up to 63% on synthetic cases.     

Influence of lamella features of UHMWPE on its physical and uniaxial tensile properties. I. Effect of sterilization method in uncrosslinked and unaged materials

The changes in the tensile toughness (U), degree of crystallinity (%C), melting temperature (Tm), lamella thickness, and lamella alignment of uncrosslinked and unaged GUR 1150HP ultra-high-molecular-weight polyethylene specimens, following different sterilization treatments (none, gamma-irradiation in air, gamma-irradiation in a nitrogen-rich atmosphere, ethylene oxide gas, and gas plasma) were determined. For each of the properties - U, %C, and Tm - the only significant difference in the mean value was found between the set of specimens gamma-irradiated in air, on the one hand, and each of the other sets, on the other hand. It was found that lamella thickness showed little change between the groups of specimens but there was a significant difference in the lamella orientation between the set of specimens that had been gamma-irradiated in air, on the one hand, and each of the other sets, on the other. It thus appears that the changes seen in the physical and mechanical properties determined may be a reflection of the change in the polymer's lamella alignment.