Does neoadjuvant hormone therapy for early prostate cancer affect cognition? Results from a pilot study

OBJECTIVE: To examine, in a prospective study, the influence that temporary reversible medical castration for localized prostate cancer has on cognition, by assessing whether temporary 3-5 month treatment with a luteinizing-hormone releasing hormone (LHRH) agonist before radical radiotherapy had a short- or long-term affect on cognitive function. PATIENTS, SUBJECTS AND METHODS: Thirty-two patients with localized prostate cancer had cognitive assessments at baseline (T1) before the start of drug treatment, at 3 months (T2) or on completing drug treatment but before radiotherapy, and 9 months later (T3). Eighteen men with no prostate cancer (controls subjects) completed the cognitive tests at the same times. In addition, psychological functioning and quality of life were assessed at the same times, together with serum free and bound testosterone, beta-oestradiol and sex hormone-binding globulin levels. RESULTS: There was a significant cognitive decline (on at least one cognitive task) at T2 in 15 (47%) patients vs three (17%) of controls (odds ratio 4.412, P = 0.033). Most patients (nine of 15) who had a change in performance declined on tasks of spatial memory and ability. At T3 there was significant cognitive decline in 11 (34%) patients and five (28%) control subjects (odds ratio 1.37, P = 0.631). CONCLUSION: This pilot study suggests that short-term LHRH therapy for early-stage prostate cancer has modest short-term consequences on men's cognitive functioning; a larger prospective study is warranted.     

The effects of adjuvant chemotherapy on cognition in women with breast cancer--preliminary results of an observational longitudinal study

Several studies have reported that chemotherapy-treated patients have impaired cognition function relative to control groups. We are conducting a longitudinal study with cognitive assessments at baseline, 6 and 18 months. A planned preliminary analysis of data from 50 chemotherapy patients and 43 healthy controls at baseline and post-treatment found a significant group by time interaction on three measures of verbal and working memory. Chemotherapy patients were more likely to show cognitive decline than controls (OR 2.25). Patients were significantly more likely to have GHQ(12) scores indicative of possible psychological morbidity and showed significant increases in endocrine symptoms and fatigue post-treatment however neither GHQ(12) nor quality-of-life variables were related to cognitive performance.     

Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight

Maintenance of a reduced body weight is accompanied by decreased energy expenditure that is due largely to increased skeletal muscle work efficiency. In addition, decreased sympathetic nervous system tone and circulating concentrations of leptin, thyroxine, and triiodothyronine act coordinately to favor weight regain. These "weight-reduced" phenotypes are similar to those of leptin-deficient humans and rodents. We examined metabolic, autonomic, and neuroendocrine phenotypes in 10 inpatient subjects (5 males, 5 females [3 never-obese, 7 obese]) under 3 sets of experimental conditions: (a) maintaining usual weight by ingesting a liquid formula diet; (b) maintaining a 10% reduced weight by ingesting a liquid formula diet; and (c) receiving twice-daily subcutaneous doses of leptin sufficient to restore 8 am circulating leptin concentrations to pre-weight-loss levels and remaining on the same liquid formula diet required to maintain a 10% reduced weight. During leptin administration, energy expenditure, skeletal muscle work efficiency, sympathetic nervous system tone, and circulating concentrations of thyroxine and triiodothyronine returned to pre-weight-loss levels. These responses suggest that the weight-reduced state may be regarded as a condition of relative leptin insufficiency. Prevention of weight regain might be achievable by strategies relevant to reversing this leptin-insufficient state.     

A correlation of catecholamine and vasoactive peptide release with hemodynamics in patients undergoing resection of arteriovenous malformations

Introduction: Control of blood pressure can be a problem for intracranial procedures. To investigate the relationship between hemodynamic variables and endogenous vasoactive substances, we studied patients undergoing resection of arteriovenous malformations (AVMs). Methods: This was a nonrandomized, prospective study of six patients who had resection of an intracranial AVM and six patients who had clipping of an intracranial aneurysm (ICA) that had not bled. Operative and postoperative blood pressure was controlled with sodium nitroprusside. Heart rate (HR), mean arterial pressure, pulmonary capillary wedge pressure, and cardiac index (CI) were measured after induction of anesthesia; before, during, and after hypotensive anesthesia; immediately postoperatively; and at 12, 24, and 36 hours postoperatively. Blood samples were drawn simultaneously in the AVM group to measure levels of norepinephrine, epinephrine, renin, aldosterone, vasopressin, angiotensin I, and angiotensin II and correlated with significant hemodynamic changes. Results: HR and CI increased significantly among patients with AVMs compared with patients with ICAs (p<0.001 and p=0.05, respectively). HR was significantly correlated with renin (r=0.60), norepinephrine (r=1.00), and vasopressin (r=0.66). CI was significantly correlated with epinephrine (r=1.00), renin (r=0.77), angiotensin II (r=0.71), and vasopressin (r=0.82). Patients with AVMs had a hyperdynamic state characterized by increases in HR and CI. These increases were accompanied by increased renin, norepinephrine, vasopressin, epinephrine, and angiotensin II serum concentrates. Conclusions: There were no significant differences in blood pressure changes between patients who had resection for AVM and those who had clipping of ICA, probably due to the use of sodium nitroprusside in the AVM group. Patients with AVMs had a hyperdynamic state with increases in epinephrine, norepinephrine, angiotensin II, plasma renin activity, and vasopressin. Whether this hyperdynamic state is caused by the resection of the AVM or the use of sodium nitroprusside (SNP) cannot be concluded. Blockage of these mediators preoperatively may help control blood pressure without sodium nitroprusside.     

Morphology and tracer coupling pattern of alpha ganglion cells in the mouse retina

Alpha cells are a type of ganglion cell whose morphology appears to be conserved across a number of mammalian retinas. In particular, alpha cells display the largest somata and dendritic arbors at a given eccentricity and tile the retina as independent on- (ON) and off-center (OFF) subtypes. Mammalian alpha cells also express a variable tracer coupling pattern, which often includes homologous (same cell type) coupling to a few neighboring alpha cells and extensive heterologous (different cell type) coupling to two to three amacrine cell types. Here, we use the gap junction-permeant tracer Neurobiotin to determine the architecture and coupling pattern of alpha cells in the mouse retina. We find that alpha cells show the same somatic and dendritic architecture described previously in the mammal. However, alpha cells show varied tracer coupling patterns related to their ON and OFF physiologies. ON alpha cells show no evidence of homologous tracer coupling but are coupled heterologously to at least two types of amacrine cell whose somata lie within the ganglion cell layer. In contrast, OFF alpha cells are coupled to one another in circumscribed arrays as well as to two to three types of amacrine cell with somata occupying the inner nuclear layer. We find that homologous coupling between OFF alpha cells is unaltered in the connexin36 (Cx36) knockout (KO) mouse retina, indicating that it is not dependent on Cx36. However, a subset of the heterologous coupling of ON alpha cells and all the heterologous coupling of OFF alpha cells are eliminated in the KO retina, suggesting that Cx36 comprises most of the junctions made with amacrine cells.     

Corticosteroids for septic shock--a standard of care?

Septic shock has a crude mortality rate of 45% and claims thelives of 90 000 people each year in the USA alone.¹ An epidemiologicalstudy from France of over 100 000 intensive care unit (ICU)admissions indicates the incidence of septic shock before orfollowing admission to ICU is rising and now affects almost10% of this patient population.² Given the scale and associatedcosts of this problem,^{3 4} it is not surprising that developingsolutions has been a focus of researchers, clinicians, and thepharmaceutical industry. Despite many past disappointments particularlywith antagonists of endogenous mediators,⁵ some recent approacheshave shown promise in prevention or treatment of sepsis     

Intensive chemotherapy with and without cranial radiation for Burkitt leukemia and lymphoma: final results of Cancer and Leukemia Group B Study 9251

BACKGROUND: The objective of the current study was to evaluate the efficacy of intensive chemotherapy with and without cranial radiation for central nervous system (CNS) prophylaxis in adults with Burkitt leukemia or lymphoma. METHODS: Patients received 18 weeks of therapy. Prophylactic cranial radiation (2400 centigrays) and 12 doses of triple intrathecal chemotherapy were administered to the first cohort of patients. A subsequent cohort received the same therapy, with the exceptions that intrathecal therapy was reduced to six doses and radiotherapy was administered only to high-risk individuals. RESULTS: The median follow-up durations were 6.8 years in Cohort 1 and 4.1 years in Cohort 2. Three occurrences of transverse myelitis, 2 severe neuropathies, 3 cases of aphasia, and 1 case of blindness were documented in the first cohort of 52 patients (Cohort 1). In the subsequent cohort of 40 patients (Cohort 2), none of these occurrences were observed, and patients experienced less neurologic toxicity overall (61% vs. 26%; P=0.001). Responses were similar, and the 3-year event-free survival rate was 0.52 (95% confidence interval, 0.38-0.65) for Cohort 1 and 0.45 (0.29-0.60) for Cohort 2. CONCLUSIONS: Intensive, short-duration chemotherapy with less intensive CNS prophylaxis led to control at this sanctuary site with little neurotoxicity and may be curative for adults with Burkitt leukemia or lymphoma.