Melphalan dosing regimens for management of recurrent melanoma by isolated limb perfusion: Application of a physiological pharmacokinetic model based on melphalan distribution in the isolated perfused rat hindlimb

The optimal dosing schedule for melphalan therapy of recurrent malignant melanoma in isolated limb perfusions has been examined using a physiological pharmacokinetic model with data from isolated rat hindlimb perfusions (IRHP), The study included a comparison of melphalan distribution in IRHP under hyperthermia and normothermia conditions. Rat hindlimbs were perfused with Krebs-Henseleit buffer containing 4.7% bovine serum albumin at 37 or 41.5 degrees C at a flow rate of 4 ml/min. Concentrations of melphalan in perfusate and tissues were determined by high performance liquid chromatography with fluorescence detection, The concentration of melphalan in perfusate and tissues was linearly related to the input concentration. The rate and amount of melphalan uptake into the different tissues was higher at 41.5 degrees C than at 37 degrees C. A physiological pharmacokinetic model was validated from the tissue and perfusate time course of melphalan after melphalan perfusion. Application of the model involved the amount of melphalan exposure in the muscle, skin and fat in a recirculation system was related to the method of melphalan administration: single bolus > divided bolus > infusion, The peak concentration of melphalan in the perfusate was also related to the method of administration in the same order, Infusing the total dose of melphalan over 20 min during a 60 min perfusion optimized the exposure of tissues to melphalan whilst minimizing the peak perfusate concentration of melphalan. It is suggested that this method of melphalan administration may be preferable to other methods in terms of optimizing the efficacy of melphalan whilst minimizing the limb toxicity associated with its use in isolated limb perfusion.

The family attitude scale: Reliability and validity of a new scale for measuring the emotional climate of families

Research on outcomes from psychiatric disorders has highlighted the importance of expressed emotion (EE), but its cost-effective measurement remains a challenge. This article describes development of the Family Attitude Scale (FAS), a 30-item instrument that can be completed by any informant. Its psychometric characteristics are reported in parents of undergraduate students and in 70 families with a schizophrenic member. The total FAS had high internal consistency in all samples, and reports of angry behaviour in FAS items showed acceptable inter-rater agreement. The FAS was associated with the reported anger, anger expression and anxiety of respondents. Substantial associations between the parents' FAS and the anger and anger expression of students was also observed. Parents of schizophrenic patients had higher FAS scores than parents of students, and the FAS was higher if disorder duration was longer or patient functioning was poorer. Hostility, high criticism and low warmth on the Camberwell Family Interview (CFI) were associated with a more negative FAS. The highest FAS in the family was a good predictor of a highly critical environment on the CFI. The FAS is a reliable and valid indicator of relationship stress and expressed anger that has wide applicability. (C) 1997 Elsevier Science Ireland Ltd.

INTENSITY-MODULATED AND 3D-CONFORMAL RADIOTHERAPY FOR WHOLE-VENTRICULAR IRRADIATION AS COMPARED WITH CONVENTIONAL WHOLE-BRAIN IRRADIATION IN THE MANAGEMENT OF LOCALIZED CENTRAL NERVOUS SYSTEM GERM CELL TUMORS

Purpose: To compare the sparing potential of cerebral hemispheres with intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for whole-ventricular irradiation (WVI) and conventional whole-brain irradiation (WBI) in the management of localized central nervous system germ cell tumors (CNSGCTs). Methods and Materials: Ten cases of patients with localized CNSGCTs and submitted to WVI by use of IMRT with or without a ""boost"" to the primary lesion were selected. For comparison purposes, similar treatment plans were produced by use of 3D-CRT (WVI with or without boost) and WBI (opposed lateral fields with or without boost), and cerebral hemisphere sparing was evaluated at dose levels ranging from 2 Gy to 40 Gy. Results: The median prescription dose for WVI was 30.6 Gy (range, 25.2-37.5 Gy), and that for the boost was 16.5 Gy (range, 0-23.4 Gy). Mean irradiated cerebral hemisphere volumes were lower for WVI with IMRT than for 3D-CRT and were lower for WVI with 3D-CRT than for WBI. Intensity-modulated radiotherapy was associated with the lowest irradiated volumes, with reductions of 7.5%, 12.2%, and 9.0% at dose levels., compared with 3D-CRT. Intensity-modulated radiotherapy provided of 20, 30, and 40 Gy, respectively statistically significant reductions of median irradiated volumes at all dose levels (p = 0.002 or less). However, estimated radiation doses to peripheral areas of the body were 1.9 times higher with IMRT than with 3D-CRT. Conclusions: Although IMRT is associated with increased radiation doses to peripheral areas of the body, its use can spare a significant amount of normal central nervous system tissue compared with 3D-CRT or WBI in the setting of CNSGCT treatment. (C) 2010 Elsevier Inc.

Orofacial granulomatosis: A diagnostic problem for the unwary and a management dilemma. Case reports

Orofacial granulomatosis is a condition that, may be difficult to diagnose for those unfamiliar with the entity. This paper describes two cases and addresses the presentation, pathogenesis and treatment. The clinical recognition of his condition is important as is the subsequent investigation by an appropriate specialist. Management of patients needs to take into account the results of further investigations, the patient's expectations, and the severity of the condition.

Factors affecting management decisions in rectal cancer in clinical practice: results from a national survey

Management of rectal cancer has become increasingly complex and a multidisciplinary approach is considered of key importance for improving outcomes. A national survey among specialists involved in this multidisciplinary setting was performed. A web-based survey containing 11 questions regarding rectal cancer management was sent to surgeons and medical oncologists registered by their corresponding societies as members. Statistical analysis was performed using the chi-square and Fisher`s exact tests for all categorical variables according to response to individual questions. Multivariate analysis was performed using Cox`s logistic regression. Overall, 418 email recipients responded the survey. Local staging was performed without either magnetic resonance imaging or endorectal ultrasound by 64% of responders. Seventy-two percent considered that final management decision should be made after neoadjuvant chemoradiation therapy. Additionally, 46% considered that an alternative procedure (local excision or observation) was appropriate in a patient with a complete clinical response. Colorectal surgeons were more frequently in favor of longer intervals after completion of chemoradiation therapy (P = 0.001) and of alternative management procedures after a complete clinical response (P = 0.02). After multivariate analysis, the choice of a watch and wait approach after a complete clinical response following neoadjuvant chemoradiation therapy was significantly more frequent among surgeons (OR 3.5, 95% CI 1.8-7.1). Surgeons seem to be more in favor of tailoring management of rectal cancer according to tumor response after neoadjuvant chemoradiation therapy, with longer intervals after chemoradiation therapy, decisions about treatment strategy being made after chemoradiation therapy instead of before, and the use of alternative surgical procedures after a complete clinical response following neoadjuvant therapy.

Test-retest reliability of isokinetic strength and endurance tests in patients with intermittent claudication

The objective was to determine the reliability of isokinetic strength and endurance testing in the ankle joints of patients with intermittent claudication. Twenty-three patients with peripheral artery disease (PAD) and symptoms of intermittent claudication participated in the study. Isokinetic strength and endurance testing of the ankle joint were performed in symptomatic and asymptomatic legs on 3 separate days. Intraclass coefficient correlation of peak torque (PT) and total work (TW) ranged from 0.77 to 0.92 and 0.89 to 0.96, respectively. PT and TW increased significantly and similarly in both legs from day 1 to day 2 (PT: +42 +/- 84% in the symptomatic leg and +33 +/- 51% in the asymptomatic leg, p < 0.05;TW: +38 +/- 26% in the symptomatic leg and +26 +/- 50% in the asymptomatic leg, p < 0.05). In conclusion, isokinetic strength and endurance testing in the ankle joints of patients with PAD presents reliability coefficients ranging from 0.77 to 0.96. However, strength and endurance increased between the first and the other test sessions performed on separate days, suggesting that two test sessions are necessary for the accurate evaluation of strength and endurance in patients with PAD.

Brazilian version of the Functional Assessment Measure: cross-cultural adaptation and reliability evaluation

The objective of this prospective study was to perform a cross-cultural adaptation of the Functional Assessment Measure (FAM) into Brazilian Portuguese, and to assess the test-retest reliability. The instrument was translated, back-translated, pretested, and reviewed by a committee. The Brazilian version was assessed in 61 brain-injury patients. Intrarater and interrater reliability was verified by a test-retest procedure (intraclass correlation). Intrarater reliability was moderate-to-excellent; interrater reliability was moderate-to-excellent, with the exception of one item. The Brazilian version of the FAM has acceptable test-retest reliability. Results suggest the use of the Brazilian version of the FAM in the Brazilian population, for disability evaluation and outcome assessment. Further research is required to evaluate the psychometric properties of the scale. International Journal of Rehabilitation Research 34:89-91 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Two-Year Outcome of Partial Lacrimal Punctal Occlusion in the Management of Dry Eye Related to Sjogren Syndrome

Purpose: To analyze the influence of thermal partial punctal occlusion on the ocular surface of dry eye related to Sjogren syndrome. Material and Methods: Thirty-seven eyes of 19 patients (3 male and 16 female; 49.11 +/- 14.33 years old) with keratoconjunctivitis sicca were enrolled in this study. Superior and inferior partial occlusion were performed in both eyes under topical anesthesia using thermal cautery with a sterile tip to obtain lacrimal punctum smaller than 0.5 mm. Schirmer I, break-up-time, diameter of lacrimal puncta, corneal fluorescein, and rose Bengal staining scores were analyzed before and after 24 weeks and after 24 months of the procedure. All measurements were performed under controlled climate. Results: The average lacrimal punctum diameter before the procedure was 0.65 +/- 0.134 mm. All lacrimal puncta were successfully reduced to less than 0.5 mm after 4 weeks of the procedure. The average Schirmer I test values improved statistically after 24 weeks and maintained stable after 24 months. Average break-up-time, rose Bengal, and fluorescein staining score values improved statistically after 24 weeks and improved even more after 24 months. Average Schirmer I test, break-up-time, rose Bengal, and fluorescein staining scores showed significant improvement (p < 0.0001) after 24 months of partial thermal punctal occlusion. Conclusion: Our study showed that reducing the punctum diameter to 0.5 mm can improve vital staining scores, break-up-time, and Schirmer I test in dry eye related to Sjogren syndrome.