An ultrasonographic study of Peyronie's disease

A study was undertaken to determine the usefulness of ultrasonography as an investigative tool, and its role in deciding the management of Peyronie's disease. Fifteen patients with Peyronie's disease were studied by ultrasonography. The plaque could be demonstrated in all patients. The dimensions of the plaque varied from less than 1 cm to more than 7cm in length and 2-4mm in thickness. The disease was active in 26% of the patients, as indicated by the presence of hypoechoic areas around a central region of hyperechoism. Ultrasonogram was more accurate than clinical assessment in delineating the extent of lesions. In one-third of the patients, sonography demonstrated the plaques to be more extensive than had been detected by clinical examination. Calcification and activity of disease (which are clearly defined by ultrasonogram) are determining factors in the management of Peyronie's disease. This information allows the surgeon to select the modality of treatment, the timing of surgery and extent of excision. Thus, ultrasonography plays a vital role in the preliminary investigation and management of Peyronie's disease.     

Autoantibodies in early seropositive rheumatoid arthritis,before and during disease modifying antirheumatic drug treatment

OBJECTIVE: Autoantibodies observed in patients with rheumatoid arthritis (RA) during clinical trials of immunomodulating agents may cause concern about possible induction of autoimmunity by the therapeutic intervention. We determined the frequency and variability of selected autoantibodies in patients with early rheumatoid factor (RF) positive RA during a prospective observational study. METHOD: The study cohort consisted of 276 patients with active RA and with RF > or = 40 IU, who were enrolled between January 1, 1993, and April 1, 2000, before starting disease modifying antirheumatic drug (DMARD) therapy (average duration of symptoms, 7 mo). During an average of 3.5 years followup, a panel of autoantibodies was determined at entry, 6 months, 12 months, and yearly thereafter, in addition to routine clinical, radiographic, and laboratory assessments. After enrollment, patients were treated with DMARD at the discretion of their rheumatologists. RESULTS: At entry before any DMARD therapy, antinuclear antibody (ANA; by HEp-2) values were negative in 31%, borderline (8 IU/ml) in 26%, and > 8 (mean 65.5 IU/ml) in 41%. Tender and swollen joint counts, Disease Activity Score, and RF values were significantly higher in those with ANA > 8. During followup 726 paired serial specimens were available; 12.5% changed from negative to positive ANA and 12.3% from positive to negative. Additional autoantibodies were present in specimens of 20% of the subjects; 8% had 2 and 1.4% had 3 other autoantibodies. Anti-dsDNA was detected in 13 (5.5%) patients; 4 changed from negative to positive and one from positive to negative. SSA IgG and SSB IgG autoantibodies were both present in one of these patients. Ribosomal P protein autoantibodies were noted in 2 other patients, but Sm (Smith) and uRNP/snRNP IgG autoantibodies were not present in any patient. No patient had a diagnosis of systemic lupus erythematosus. Antithyroid peroxidase (20 patients), parietal cell (15), smooth muscle (14), reticulin (9), mitochondrial (5), striational (2), SSB (2) and SCL-70 (1) autoantibodies were detected in some specimens. Seven patients were diagnosed with hypothyroidism, one with chronic thyroiditis, one with hepatitis C, and 9 with malignancies. CONCLUSION: In patients with early RF positive RA the frequent occurrence of autoantibodies before and during treatment with standard DMARD may make it difficult to attribute their presence to new therapies.     

Phase I, pharmacokinetic, and biological study of erlotinib in combination with paclitaxel and carboplatin in patients with advanced solid tumors.

PURPOSE: To assess the feasibility of administering erlotinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, in combination with paclitaxel and carboplatin, and to identify pharmacokinetic interactions, evaluate downstream effects of EGFR inhibition on surrogate tissues, and seek preliminary evidence for clinical activity. EXPERIMENTAL DESIGN: Patients with advanced solid malignancies were treated continuously with erlotinib at doses of 100, 125, and 150 mg/d orally along with fixed i.v. doses of paclitaxel 225 mg/m(2) and carboplatin AUC 6 mg x min/mL, both on day 1 every 3 weeks. RESULTS: Twenty evaluable patients were treated with 136 courses of erlotinib, paclitaxel, and carboplatin. Myelosuppression, skin rash, and diarrhea were the principal toxicities. Dose limiting diarrhea occurred in 1 of 6 patients at the 100 mg erlotinib dose level, whereas 0 of 9 evaluable patients at the 125 mg erlotinib dose level experienced dose limiting toxicity and 3 of 5 evaluable patients at 150 mg erlotinib experienced dose limiting skin rash and neutropenic sepsis. There was no evidence of pharmacokinetic interactions between paclitaxel and erlotinib; however, total carboplatin exposure trended higher in the presence of erlotinib. No consistent downstream effects on EGFR inhibition were found in skin. Durable objective responses were observed in non-small-cell lung and head and neck cancers. CONCLUSIONS: A dose level of erlotinib 125 mg combined with paclitaxel 225 mg/m(2) and carboplatin AUC 6 mg.min/mL is recommended for disease-directed studies. This phase I trial was followed by a randomized phase III study in non-small-cell lung cancer using a similar regimen.     

Preoperative embolization of a large vaginal leiomyoma: Report of a case and review of the literature

Leiomyoma of the vagina is a very rare tumour of the lower urogenital tract. These slow‐growing masses may be asymptomatic or present with pain, dyspareunia or urinary symptoms. Rarely, these tumours may present with life‐threatening haemorrhage. These hypervascular tumours are treated by surgical excision. Preoperative embolization therefore may aid in devascularization of these tumours before surgical excision. We present the MRI features of a case of vaginal leiomyoma, which was managed by preoperative embolization and was then excised in toto. To the best of our knowledge, this is the first report where preoperative embolization was performed before excision of a vaginal leiomyoma with minimal peroperative blood loss.     

Paracetamol use, availability, and knowledge of toxicity among British and American adolescents

Paracetamol is the commonest agent employed in self poisoning, however it is not clear whether adolescents possess insight into the serious complications associated with its misuse. Using a one page questionnaire, the availability, usage, and knowledge of toxicity of paracetamol among 1147 American and British adolescents was assessed. Although 90% of all students recognised that paracetamol could kill, the great majority of students overestimated the lethal dose. In addition, while knowledge regarding side effects of paracetamol was poor the drug was widely available to, and used by, the study population. It is proposed that gross overestimation of the number of tablets required to kill, poor understanding of paracetamol side effects, and wide availability of the drug contribute to its frequent use in adolescent suicidal behaviour. The inclusion of some over-the-counter medications in school drug education programs in addition to tighter control of the availability of paracetamol may help reduce the problem of adolescent self poisoning.     

Subject-by-Formulation Interaction in Bioequivalence: Conceptual and Statistical Issues

Purpose. The FDA has proposed replacing the current averagebioequivalence criterion with population and individual bioequivalence criteriathat consider variances in addition to the difference of averages. Oneof these variances in the individual bioequivalence criterion measuressubject-by-formulation interaction, the extent to which thetest-reference difference varies from person to person. This paper discussesconceptual and statistical issues raised in various publications andpresentations with respect to the presence and estimation of such aninteraction. Methods. We focus on the importance of subject-by-formulationinteraction, an understanding of what is a large interaction, and theassessment of the magnitude of this interaction in bioequivalence studies.Simulation studies, examples from the literature, and data from FDAfiles are used to demonstrate the magnitude of the interaction and itsdistribution under various conditions. Results. The concept of a large interaction is tied to the concept of alarge mean difference. We suggest that an interaction greater than0.15 is a conservative criterion for a large interaction. Magnitudes ofestimated interaction are affected by variability, sample size, and theselection of data sets that pass average bioequivalence. Conclusions. Examples of substantial interactions are beginning toappear. More data is needed before reaching definitive conclusionsregarding the frequency and importance of observed interactions.     

Uterine leiomyomas in the infertile patient: preoperative localization with MR imaging versus US and hysterosalpingography

Eleven women with a history of infertility and uterine leiomyomas underwent magnetic resonance (MR) imaging of the pelvis prior to myomectomy. Nine also underwent preoperative pelvic ultrasonography (US), and ten underwent hysterosalpingography. All studies were interpreted prospectively by independent observers. With each imaging modality, the location (one of 11 anatomic segments), size, and appearance of detected uterine leiomyomas were determined and compared with surgical and histologic findings. Among the nine patients who underwent both MR and US, the sensitivity (85%) and accuracy (94%) of MR imaging for abnormal segments was significantly better than that of US (sensitivity = 69%, P = .015; accuracy = 87%, P = .043). For the ten patients who underwent both MR and hysterosalpingography, the sensitivity (91%) and accuracy (96%) of MR imaging was better than that of hysterosalpingography (sensitivity = 18%, P = .0005; accuracy = 72%, P = .0005). The specificities of the three modalities did not significantly differ (100%, 97%, and 98% for MR, US, and hysterosalpingography, respectively). These data suggest that MR imaging is superior to US or hysterosalpingography for preoperatively locating uterine leiomyomas.