Verbal fluency and executive dysfunction in amyotrophic lateral sclerosis (ALS)

Neuropsychological investigations of amyotrophic lateral sclerosis (ALS) patients have revealed variable results on specific tests, despite a similar overall cognitive profile of predominantly executive dysfunction with some evidence of memory impairment. The most striking and consistent deficit is found using tests of verbal fluency. The current investigation explored why verbal fluency is particularly sensitive to the impairment in ALS, by investigating some of the underlying cognitive processes: (i) intrinsic response generation; (ii) phonological loop functions; and (iii) simple word retrieval. Twenty-two ALS patients and 25 healthy controls were investigated. The battery included: (i) written and spoken letter-based fluency, category fluency, design fluency; (ii) the Phonological Similarities effect and Word Length Effect; and (iii) computerised sentence completion and confrontational naming. The tests were designed to control for motor speed and to accommodate for the range of disabilities that are present in ALS patients. Significant impairments were found on some tests of intrinsic response generation, namely the Written Verbal Fluency Test, Category Fluency Test (generation of animal names) and Design Fluency Test. Phonological loop functions appeared to be intact with evidence of both the Phonological Similarities and Word Length Effects, but the ALS patients displayed significantly reduced working memory capacity. No deficits were found on tests of simple word retrieval. The findings indicate that verbal fluency impairments in ALS patients result from a higher order dysfunction, implicating deficits in the supervisory attentional system or central executive component of working memory, and are not caused or exaggerated by an impairment in phonological loop functions or in primary linguistic abilities. The study also demonstrates the importance of controlling for differences in motor speed, which may have served to exaggerate the presence of cognitive deficits in ALS patients reported by some other studies.     

Imaging of the symptomatic type II accessory navicular bone

Accessory ossicles of the foot are commonly mistaken for fractures. The accessory navicular is one of the most common accessory ossicles of the foot. There is a higher incidence in women and the finding might be bilateral in 50?90%. This entity is usually asymptomatic, although populations with medial foot pain have a higher prevalence. Three types of accessory navicular bone have been described. The type II accessory navicular is the most commonly symptomatic variant with localized chronic or acute on chronic medial foot pain and tenderness with associated inflammation of overlying soft tissues. Plain radiographic identification of the accessory navicular is insufficient to attribute symptomatology. Ultrasound allows for comparison with the asymptomatic side and localization of pain. Bone scintigraphy has a high sensitivity but positive findings lack specificity. Magnetic resonance imaging is of high diagnostic value for demonstrating both bone marrow and soft tissue oedema.     

Reduced expression of the small leucine-rich proteoglycans, lumican, and decorin is associated with poor outcome in node-negative invasive breast cancer.

PURPOSE: To examine the prognostic significance of lumican and decorin, two abundant small leucine-rich proteoglycans in breast tissue stroma. EXPERIMENTAL DESIGN: Lumican and decorin expression was examined in a cohort of 140 invasive breast carcinomas by Western blot analysis. All cases were axillary lymph node-negative and treated by adjuvant endocrine therapy. RESULTS: Lumican and decorin expression was highly correlated (r = 0.45, P < 0.0001), but although low levels of lumican were associated with large tumor size (P = 0.0496), negative estrogen receptor (P = 0.0024) and progesterone receptor status (P = 0.0116), and increased host inflammatory response (P = 0.0077), low decorin levels were associated only with large tumor size (P = 0.0496). However, using univariate analysis, low levels of lumican and decorin were both associated with a shorter time to progression (P = 0.0013 and 0.0262) and poorer survival (P = 0.001 and 0.0076). In multivariate analysis using the Cox regression model, low decorin was also shown to be an independent predictive factor for recurrence (hazard ratio 2.25: 95% confidence interval 1-5, P = 0.047) and survival (hazard ratio 3.39: 95% confidence interval 1.2-9.6, P = 0.021). CONCLUSIONS: These results suggest that low levels of small leucine-rich proteoglycans in breast tumors may be associated with a worse prognosis in lymph node-negative invasive breast carcinomas and warrant further study with larger patient cohorts.     

Improved freedom from PSA failure with whole pelvic irradiation for high-risk prostate cancer

Purpose: To determine the impact of whole pelvic irradiation on the risk of PSA failure in prostate cancer patients, at high predicted risk for lymph node involvement, receiving definitive radiotherapy.

Materials and Methods: Between October 1987 and December 1995, 506 patients with clinically localized prostate cancer were treated with definitive radiotherapy at UCSF and affiliated institutions. Treatment consisted of 4-field whole pelvic irradiation followed by a prostate-only boost, or prostate-only treatment (median follow-up was 35 months and 30 months, respectively). PSA failure was defined as: 1. a PSA value ≥ 1 ng/ml; or 2. a PSA value that rose ≥ 0.5 ng/ml in ≤ 1 year posttreatment on two consecutive measurements, with the first rise defined as the time of failure. The calculated risk of lymph node positivity (%rLN+) was defined as (iPSA) + 10(GS-6), and high risk was defined as %rLN+ ≥ 15%. Univariate and multivariate analyses were performed.

Results: A total of 201 high-risk patients were identified. High-risk patients who received whole pelvic irradiation had significantly improved freedom from PSA failure compared to those who received prostate-only treatment (median PFS = 34.3 months vs. 21.0 months; p = 0.0001). Potential confounding variables, including initial PSA, Gleason score, T stage, radiation dose, year of treatment, use of three-dimensional (3D) conformal techniques, and use of hormone therapy, did not account for the observed difference in time to PSA failure. Multivariate analysis revealed type of radiation treatment to be the most significant independent predictor of outcome.

Conclusion: Whole pelvic radiotherapy significantly improves the PSA failure-free survival in patients with a high calculated risk of lymph node positivity.     

Life Extension Research: Health, Illness, and Death

Scientists, bioethicists, and policy makers are currently engaged in a contentious debate about the scientific prospects and morality of efforts to increase human longevity. Some demographers and geneticists suggest that there is little reason to think that it will be possible to significantly extend the human lifespan. Other biodemographers and geneticists argue that there might well be increases in both life expectancy and lifespan. Bioethicists and policy makers are currently addressing many of the ethical, social, and economic issues raised by life extension research. However, the emphasis on philosophical argument supporting or condemning efforts to increase human longevity means that much less attention is currently being given to the factors that might play a role in generating interest in efforts to increase human longevity. This analysis considers three factors that might play a role in heightening public interest in efforts to develop biomedical technologies capable of retarding or reversing aging processes. While discussions of life extension research can seem quite futuristic and impractical, there are some powerful existential factors that might well generate considerable public support for life extension strategies if effective biomedical interventions emerge. Rather than providing philosophical justifications supporting or condemning efforts to increase human longevity, this essay seeks to promote a better understanding of the factors generating contemporary interest in prolonging life and postponing death.     

Minimally invasive surgery for primary hyperparathyroidism: systematic review

HYPOTHESIS: Use of minimally invasive parathyroidectomy techniques, either unilateral or endoscopic, will result in the same or improved safety and efficacy outcomes as those of the bilateral open neck exploration technique in patients with primary hyperparathyroidism. DATA SOURCES: Studies on minimally invasive parathyroid surgery were identified using MEDLINE (January 1984 to August 1998), EMBASE (January 1974 to August 1998), and Current Contents (week 1 of 1993 to week 34 of 1998). The search terms were as follows: ((endoscop* or (minimal* and invasive) or unilateral) and parathyroid). The Cochrane Library was searched from issue 1 of 1966 to issue 3 of 1998, using the search terms "parathyroidectomy or parathyroid resection." STUDY SELECTION: Human studies of patients with primary hyperparathyroidism using unilateral or endoscopic exploration were included. Animal studies describing minimally invasive technique development were also included. A surgeon (R.F.P.) and researcher (W.J.B.) independently assessed the retrieved articles for their inclusion in the review. DATA EXTRACTION: Studies directly comparing the unilateral method with bilateral open neck exploration were used to analyze outcomes. DATA SYNTHESIS: Analysis of data using odds ratios and 95% confidence intervals indicated a tendency to favor the unilateral technique. However, these individual studies generally had large confidence intervals; therefore, preference to the unilateral procedure cannot be espoused with certainty. There is also a selection bias due to the strict enrollment criteria for unilateral surgery. CONCLUSIONS: The proposed role of minimally invasive parathyroid surgery is for patients with primary hyperparathyroidism who have unilateral parathyroid pathological features. To assess the safety and efficacy of minimally invasive techniques, it is suggested that their introduction be monitored as part of a trial in Australia, from which data should be accrued to a register.     

Combination gemcitabine, platinum, and bevacizumab for the treatment of recurrent ovarian cancer

ObjectiveTo describe the response rate (RR), progression-free survival (PFS), and toxicity profile of combination gemcitabine, platinum, and bevacizumab (GPB) for the treatment of recurrent epithelial ovarian cancer (EOC).MethodsA chart review of all patients with recurrent EOC who were treated with D1, D15 GPB in a 28-day cycle at a single institution was performed. Standard doses were gemcitabine 1000 mg/m², cisplatin 30 mg/m² or carboplatin AUC 3, and bevacizumab 10 mg/kg. All patients were analyzed for toxicity. RR and PFS were assessed in all patients who received at least 2 cycles of GPB.ResultsThirty-five patients were identified, and 33 received at least 2 cycles of GPB. The majority of patients (80%) were platinum sensitive. Patients received a median of 6 cycles of GPB (range 1–24). Sixteen patients (48%) had a complete response (CR), and 10 patients (30%) had a partial response (PR), for a total RR of 78%. An additional 5 patients (15%) had stable disease, and only 2 (6%) patients had progressive disease. The median overall PFS was 12 months (95% CI 7–15), with a median follow-up time of 10 months (2–22). Two patients (6%) had bowel perforations, and both survived. Hematologic toxicities were most common, with 29% and 14% of patients experiencing grade 3 or 4 neutropenia and thrombocytopenia respectively.ConclusionsThe combination of GPB demonstrated excellent efficacy for the treatment of recurrent EOC. However, serious toxicities occurred, and the safety profile of this combination requires further study.