Retrospective analysis of the efficacy and safety of once-daily tadalafil in patient subgroups: men with mild vs moderate ED and aged <50 vs 50 years.

The aim of this post-hoc pooled-data analysis was to evaluate the effects of once-daily tadalafil in men with mild or moderate ED and aged <50 or 50 years. Data from three randomized controlled trials were analyzed. Analysis of covariance models included a term for ED severity and age group. The three coprimary outcome measures in the base studies were changes from baseline to end point in the mean International Index of Erectile Function Erectile Function (IIEF-EF) domain score and the mean per-patient percentage successful vaginal penetration and intercourse attempts. Irrespective of baseline severity, once-daily tadalafil 5 mg for 12 weeks compared with placebo significantly increased the mean: (1) IIEF-EF by 6.8; (2) percent successful penetration attempts from 70.1 to 91.3%; and (3) percent successful intercourse attempts from 33.4 to 76.8% (each P<0.001). Treatment-by-age-group interaction P-values for all three coprimary efficacy end points exceeded 0.10, indicating that tadalafil treatment effects did not differ by age <50 vs 50 years. Tadalafil was generally well tolerated.

Response to treatment with tadalafil in men with erectile dysfunction who reported no successful intercourse attempts at baseline.

The purpose of this post hoc analysis was to evaluate response to tadalafil in patients with erectile dysfunction (ED) who reported failures in all sexual intercourse attempts before treatment. In a multicenter, open-label study, 1911 men received tadalafil 20 mg dosed as needed (up to once daily), for 12 weeks following a 4-week treatment-free run-in period. Efficacy measures included the sexual encounter profile (SEP) and the erectile function (EF) domain of the International Index of Erectile Function (IIEF-EF). Approximately, one-half (n=952, 49.9%) of the patients reported no successful intercourse attempts during the 4-week run-in period. Of these, 771 patients (81.0%) had at least one successful intercourse attempt during the treatment period. Furthermore, among responders, mean IIEF-EF scores at study end were similar regardless of success or no success at baseline. Patients who are unable to have successful intercourse should be encouraged to try oral phosphodiesterase type 5 inhibitor treatment for ED.

Predicting surgical outcome in temporal lobe epilepsy patients using MRI and MRSI.

OBJECTIVE: To develop a classifier that uses MR data to predict surgical outcome in patients with temporal lobe epilepsy (TLE). METHODS: Eighty-one patients with medically refractory TLE who underwent surgical treatment were studied. Patients underwent comprehensive presurgical investigation, including ictal video-EEG recording, 1H MRS imaging, and volumetric MRI. Outcome was measured using Engel's classification system, condensed into two outcome groups. Two approaches were taken. First, outcome was defined as experiencing worthwhile improvement with >90% reduction of seizure frequency (Classes I, II, and III) or not (Class IV). A second approach was to define outcome as experiencing freedom from seizures following surgery (Class I) or not (Classes II, III, and IV). For each approach, a Bayesian classifier was constructed to predict outcome by calculating the probability of a patient's pattern of results from spectroscopic analysis of the temporal lobes and volumetric analysis of the amygdala and hippocampus being associated with the various outcome groups. RESULTS: The worthwhile improvement classifier correctly predicted the surgical outcomes of 60 of 65 (92%) of patients who experienced worthwhile improvement and 10 of 16 (63%) of patients who did not. The seizure-free classifier correctly predicted the surgical outcomes of 39 of 52 (75%) of patients who became seizure free and 21 of 29 (72%) of patients who did not. CONCLUSION: MR features are important markers of surgical outcome in patients with TLE and can provide assistance in identifying surgical candidates.

Prevention of prostate cancer.

Strategies for reducing the occurrence of prostate cancers will be critical in limiting the morbidity and mortality of this disease. The long latency period of prostate tumors and improved understanding of prostate carcinogenesis suggest opportunities for effective preventive measures. Because androgen is integral to prostatic carcinogenesis, several preventive strategies under investigation target the androgen axis. Epidemiologic and basic studies implicate dietary factors in prostate cancer development and suggest that altering diet may influence prostate cancer risk and progression. Many of the micronutrients with preventive potential have antioxidant properties; cellular defenses against oxidative stresses are likely to be crucial in reducing prostate carcinogenesis. This article summarizes the current status and opportunities in prostate cancer prevention.

Limitations of transperineal ultrasound-guided prostate biopsies.

OBJECTIVES: Screening and diagnosing prostate cancer in men who have undergone abdominoperineal resection (APR) poses a diagnostic challenge. Transperineal ultrasound is an effective imaging technique, but the sensitivity of transperineal needle biopsy under ultrasound guidance has not been evaluated. We compared the results of transrectal ultrasound-guided (TRUS) biopsies and transperineal ultrasound-guided (TPUS) biopsies obtained from patients with known prostate cancer, to evaluate the accuracy of TPUS prostate biopsies. METHODS: Twenty patients with prostate cancer diagnosed by TRUS-guided biopsies were studied. Immediately before radical prostatectomy, TPUS was performed in the lithotomy position and six TPUS-guided biopsies were obtained. Routine sextant TRUS-guided biopsies were then obtained. Finally, radical retropubic prostatectomy was performed and the results of both biopsy sets were compared with the pathologic features of the surgical specimen. RESULTS: All 20 prostates contained adenocarcinoma. The prostate was well visualized with TPUS and TRUS in all cases. TPUS-guided biopsies detected cancer in only 2 of the 20 specimens, yielding a sensitivity of 10%. On the same specimens, TRUS-guided biopsies were positive in 13 of 20 cases, a sensitivity of 65%. Cancers detected by TPUS-guided biopsies tended to have a higher volume, higher Gleason grade, and higher prostate-specific antigen level than those not detected by TPUS-guided biopsies. CONCLUSIONS: TPUS-guided sextant biopsies are less accurate than TRUS-guided sextant biopsies in detecting prostate cancer, even in the hands of experienced ultrasonographers. The limitations of TPUS-guided needle biopsies emphasize the importance of screening for prostate cancer before APR.

Model-based 3-D segmentation of multiple sclerosis lesions in magnetic resonance brain images.

Human investigators instinctively segment medical images into their anatomical components, drawing upon prior knowledge of anatomy to overcome image artifacts, noise, and lack of tissue contrast. The authors describe: 1) the development and use of a brain tissue probability model for the segmentation of multiple sclerosis (MS) lesions in magnetic resonance (MR) brain images, and 2) an empirical comparison of the performance of statistical and decision tree classifiers, applied to MS lesion segmentation. Based on MR image data obtained from healthy volunteers, the model provides prior probabilities of brain tissue distribution per unit voxel in a standardized 3-D "brain space". In comparison to purely data-driven segmentation, the use of the model to guide the segmentation of MS lesions reduced the volume of false positive lesions by 50-80%

Micrometastasis in bone marrow in breast cancer.

Bone marrow trephine biopsy (BMB) was done in 57 consecutive cases of breast cancer in order to detect micrometastasis. In 46 cases, presenting for the first time, tumor cells were seen in the bone marrow in nine (19.5%) cases. Out of 11 cases who presented with recurrence, micrometastasis was detected in seven (63.6%). Bone marrow aspiration (BMA) could detect only two of these sixteen positive cases. Immuno peroxidase staining or Epithelial Membrane Antigen (EMA) helped picked up three cases which were negative on routine Hematoxylin and Eosin (H&E) stain. BMB is indicated in the evaluation of breast cancer at diagnosis and at relapse.

Ceramide 1-phosphate phosphatase activity in brain.

Recent studies have implicated sphingolipids in a variety of intracellular signaling systems. The finding that a calcium-stimulated ceramide kinase copurifies with neurotransmitter-containing vesicles suggests that ceramide, or one of its metabolites, has a role in neurotransmitter release. As a step toward understanding the role of ceramide kinase in vesicle functioning, this study sought to determine the metabolic fate of the product, ceramide 1-phosphate. We report that ceramide 1-phosphate is not deacylated by brain ceramidases to produce sphingosine 1-phosphate. It is, however, the substrate for a phosphatase activity that we name ceramide 1-phosphate phosphatase (CPPase). Subcellular fractionation studies suggest that CPPase is found in the synaptic terminal and is associated with both synaptic vesicle and plasma membranes. Divalent cations, most notably calcium, inhibit CPPase activity although not at concentrations that activate ceramide kinase. The existence of both ceramide kinase and CPPase activities at the synapse suggests that ceramide 1-phosphate production regulates some aspect of synaptic vesicle functioning.

SV2, a brain synaptic vesicle protein homologous to bacterial transporters.

Synaptic vesicle protein 2 (SV2) is a membrane glycoprotein specifically localized to secretory vesicles in neurons and endocrine cells. As a first step toward understanding the function of SV2 in neural secretion, a rat brain complementary DNA (cDNA) that encodes SV2 was isolated and characterized. Analyses of this cDNA predict that SV2 contains 12 transmembrane domains. The NH2-terminal half of the protein shows significant amino acid sequence identity to a family of bacterial proteins that transport sugars, citrate, and drugs. Expression of the SV2 cDNA in COS cells yielded a high level of SV2-like immunoreactivity distributed in a reticular and punctate pattern, which suggests localization to intracellular membranes. Its localization to vesicles, predicted membrane topology, and sequence identity to known transporters suggest that SV2 is a synaptic vesicle-specific transporter.

Serum soluble interleukin-2 (IL-2) receptor levels in women with breast carcinoma and its correlation with IL-2 receptor expression on blood lymphocytes and lymphocytic infiltration within the tumour.

This study describes serum levels of soluble interleukin-2 receptor (sIL-2R) in 13 healthy women, 10 women with breast dysplasia and 37 patients with breast carcinoma. A difference was found between sIL-2R levels in normal women and cancer patients. sIL-2R increased with the advance in stage of cancer but the extent of increase fell from stage III to stage IV as compared to the change from stage II to stage III. Of the 15 patients who were followed after surgery and/or therapy, 10 (67%) showed a fall in the serum sIL-2R levels. A negative correlation was found between sIL-2R levels and lymphocytic infiltration only within the malignant tissue. These findings probably indicate that sIL-2R exerts an immunomodulatory effect on blood lymphocytes by preventing their infiltration into the tumour tissue. To our knowledge, this is the first report of its kind in immunology of breast carcinoma.

Immunologic tools to decipher efficacy of BCG immunotherapy in advanced breast cancer: a one year follow up study.

We report the clinical outcome of conventional therapy and BCG immunisation therapy for 40 patients with advanced breast carcinoma. The clinical outcome was better for the 20 patients receiving BCG immunisation therapy. All patients were assessed for cell mediated immunologic competence before starting treatment and after completion of treatment. Thereafter they were followed for one year. Those patients who showed good local response to BCG vaccination before starting therapy had better prognosis, and those for whom anergy to PPD and DNCB could be reversed by BCG immunotherapy showed clinical improvement. Another interesting finding was that IgA was the predominating immunoglobulin located in normal breast tissue and benign breast tumours while IgG was deposited in most of the malignant breast tumour. This indicated that malignant tumours of the breast jeopardise the secretory immune system of the mammary gland.

A method for selecting constrained hand-printed character shapes for machine recognition.

Since handwritten characters vary in shape and writing-stroke sequence, it is desirable to develop a standard set of characters that are of high quality, so that not only are they easy to write, but they are also most suitable for machine recognition. A database of more than 100 000 alphanumeric patterns was assembled. It consisted of 174 models of the alphanumeric characters written by both left-handed and right-handed subjects. Based on frequency density and distance measurements, a nietric called the dispersion factor was computed to rank the various models. The principle of the metric is discussed, and results are given indicating the high quality models of the alphanumerics.

Leydig-cell tumour of the testis.

Leydig cell tumor of the testis is an uncommon occurrence. A case is reported here which had two interesting features. One was extensive calcification and the other an abundant lipid deposition within the tumour cells. The pathogenesis of calcification is discussed.

The sensitivity of the modified viterbi algorithm to the source statistics.

The modified Viterbi algorithm is a powerful, and increasingly used, tool for using contextual information in text recognition in its various forms. As yet, no known studies have been published concerning its robustness with respect to source statistics. This paper describes experiments performed to determine the sensitivity of the algorithm to variations in source statistics. The results of the experiments show that a character-recognition machine incorporating the modified Viterbi algorithm, using N-gram statistics estimated from source A does not deteriorate in performance when operating on a passage from source B even if A and B differ significantly in N-gram distributions or entropy.

Experiments in text recognition with the modified viterbi algorithm.

In this paper a modification of the Viterbi algorithm is formally described, and a measure of its complexity is derived. The modified algorithm uses aheuristic to limit the search through a directed graph or trellis. The effectiveness of the algorithm is investigated via exhaustive experimentation on an input of machine-printed text. The algorithm assumes language to be a Markov chain and uses transition probabilities between characters. The results empirically answer the long-standing question of what is the benefit, if any, of using transition probabilities that depend on the length of a word and their position in it.