Altered functional status of the hypothalamic dopaminergic tone in patients with chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a pilot study.

We compared the functional status of the hypothalamic dopaminergic tone in patients given an allogeneic hematopoietic stem cell transplantation (allo-HSCT) with chronic graft-versus-host disease (GVHD) with that observed in patients with allo-HSCT without chronic GVHD and in healthy controls. The effect of acute dopaminergic blockade with intravenous metoclopramide on serum prolactin (PRL) concentrations was evaluated. Twenty volunteers, 20 to 52 years of age, seronegative for both hepatitis C virus and the human immunodeficiency virus, were studied: (1) 10 clinically healthy men (group 1), and (2) 9 patients with leukemia, and 1 patient with refractory aplastic anemia who underwent allo-HSCT, 5 of whom (3 men and 2 women) developed chronic GVHD (group 2), and 5 (3 men and 2 women) who did not develop chronic GVHD (group 3). Serum PRL concentrations were measured both fasting and after intravenous administration of metoclopramide (10-mg bolus). The area under the PRL curve was calculated. Patients in group 2 were older than those in groups 1 and 3 (P<.018), but their body mass index was similar. Fasting serum PRL concentrations were similar among the 3 groups; however, group 2 had higher PRL concentrations throughout the test (P<.001) and a greater area under the PRL curve than groups 1 and 3 (P<.001), without differences between the last 2 groups. The differences remained significant after adjustment for age (P<.01). Our results in a small group of patients with chronic GVHD after allo-HSCT suggest the existence of an increased functional level of their hypothalamic dopamine tone, which would favor a tendency toward a diminished endogenous production, release of pituitary PRL, or both. This could represent an adaptive mechanism aiming to maintain circulating PRL concentrations within a physiological range.     

The origin and nature of stromal osteoclast-like multinucleated giant cells in breast carcinoma: implications for tumour osteolysis and macrophage biology

The origin and nature of osteoclast-like multinucleated giant cells (OMGCs), in extraskeletal neoplasms, is uncertain. The ultrastructure, antigenic phenotype and function of OMGCsm in a breast carcinoma were studied in order to clarify the relationship between OMGCs, osteoclasts and other cells of the mononuclear phagocyte system (MPS). OMGCs resorbed cortical bone in a manner similar to osteoclasts. However, unlike osteoclasts, OMGCs did not possess a ruffled border or clear zone, and expressed HLA-DR and Fc receptors and CD14, CD16, CD18 and CD11 (p150,95) antigens. In addition, OMGCs failed to respond morphologically to calcitonin and were directly stimulated by parathyroid hormone (PTH) to increase bone resorption. These findings suggest that OMGCs are a specific type of macrophage polykaryon distinct from both osteoclasts and other types of inflammatory polykaryon. Occasional smaller (20-25 microns) macrophage-like cells were also associated with resorption pits. Bone resorption by OMGCs isolated from the breast indicates that a cell of the MPS can be transplanted to a new tissue location and perform a highly specialised function appropriate to an MPS cell of that tissue (i.e. the osteoclast). PTH stimulation of bone resorption by OMGCs suggests that PTH or a PTH-like protein, may be involved in the bone resorption and consequent hypercalcaemia associated with metastatic breast cancer.     

The Effect of Flurbiprofen on Steady-State Plasma Lithium Levels

Study Objective . To evaluate the effects of flurbiprofen therapy on the pharmacokinetics of lithium. Design . Placebo-controlled, single-blind, crossover study. Setting . University-affiliated hospital. Patients . Eleven healthy women with bipolar disorder. Interventions . The subjects received therapeutic doses of lithium administered as an immediate-release capsule every 12 hours. In addition, they received one placebo tablet every 12 hours during phase I and flurbiprofen 100 mg every 12 hours during phase II of the study. Measurements and Main Results . Steady-state pharmacokinetic parameters were measured for each phase. Lithium trough plasma concentration (C_min) and area under the curve were statistically significantly increased (p<0.05) when patients received flurbiprofen. Flurbiprofen also caused decreases in lithium clearance and 24-hour lithium urine excretion, although the changes did not reach statistical significance. Clinically significant increases in C_min appeared to be associated with a greater than 1000-μg/24 hour decrease in urinary excretion of prostaglandin E₂. Conclusion . Patients with clinically normal renal function may experience an increase in lithium levels with the initiation of flurbiprofen therapy.     

Aversion to risk and guilt

Much research has shown that cognitive processes are largely guided by individuals' states of mind (Mancini & Gangemi, 2002a, in press; Smeets, de Jong, & Mayer, 2000). In this paper, we specifically consider a state of mind characterized by guilt for having acted irresponsibly. This state is currently considered the breeding ground for the obsessive–compulsive disorder (Rachman, 2002; Salkovskis & Forrester, 2002). Our aim is to examine the impact of this state of mind on decision under risk. We hypothesize that individuals' choices (risk seeking/risk aversion) depend on how they evaluate themselves, as guilty or as victims of a wrong, and thus on moral values. People who evaluate them‐selves as guilty are expected to show a risk‐averse preference. People who evaluate themselves as victims are expected to show a risk‐seeking preference. In two different experiments, we demonstrated that non‐clinical participants' aversion to risky choices and preference for risky choices vary as a function of their moral role (guilty/victim). As predicted, in both the experiments, participants experienced intolerance for risk, making more riskless choices, in the context of guilt. Thus, aversion to risk‐taking is actually affected by a mental state of guilt. Copyright © 2004 John Wiley & Sons, Ltd.     

Role of fine-needle aspiration cytology and needle-core biopsy in the diagnosis of lobular carcinoma of the breast

Fine-needle aspiration cytology (FNAC) plays a key role in the preoperative diagnosis of carcinoma of the breast but is less reliable in the diagnosis of infiltrating lobular carcinoma. The method of diagnosis was reviewed in 56 patients with lobular carcinoma who had attended screening and symptomatic clinics. In 29 patients FNAC results demonstrated malignant cells; 15 of these had palpable disease and the mean tumour size was 21 mm. In 27 patients FNAC failed to demonstrate malignant cells; 13 lesions were palpable and the mean tumour size was 23 mm. Ten patients were diagnosed by needle-core biopsy when FNAC was not diagnostic. FNAC may fail to diagnose even large lobular carcinoma and needle-core biopsy is strongly recommended in this situation.     

Temporal relationship of hepatocellular dysfunction and ischemia in sepsis

To determine whether hepatic dysfunction in sepsis results from hypoperfusion or direct cellular injury, Sprague-Dawley rats underwent either cecal ligation and puncture or sham operation. After either two or six hours, effective hepatic blood flow was measured using the galactose clearance method. Hepatocytes were isolated and intracellular sodium and potassium and glucose production were measured. Hepatic blood flow in septic rats decreased as early as two hours after sepsis when compared with sham-operated rats (3.8 +/- 1.4 vs 8.7 +/- 3.1 mL/min/100 g body weight). Intracellular sodium and potassium levels and glucose production in septic rats were not significantly different when compared with controls at two hours. After six hours, hepatic blood flow remained depressed and intracellular sodium level was increased compared with sham-operated rats (41.7 +/- 10.4 vs 31.4 +/- 5.9 mmol/L [41.7 +/- 10.4 vs 31.4 +/- 5.9 mEq/L]) and potassium decreased compared with controls (90.7 +/- 7.9 vs 111.5 +/- 6.7 mmol/L [90.7 +/- 7.9 vs 111.5 +/- 6.7 mEq/L]). Glucose production was decreased in septic rats after six hours when compared with controls (4.7 +/- 1.5 vs 15.4 +/- 6.4 mumol/g hepatocytes). These data suggest that hepatic blood flow is decreased before alterations in intracellular sodium and potassium as well as glucose production.     

Magnetic resonance elastography of the lung: technical feasibility.

Magnetic resonance elastography (MRE) is a phase-contrast technique that can spatially map shear stiffness within tissue-like materials. To date, however, MRE of the lung has been too technically challenging-primarily because of signal-to-noise ratio (SNR) limitations and phase instability. We describe an approach in which shear wave propagation is not encoded into the phase of the MR signal of a material, but rather from the signal arising from a polarized noble gas encapsulated within. To determine the feasibility of the approach, three experiments were performed. First, to establish whether shear wave propagation within lung parenchyma can be visualized with phase-contrast MR techniques, MRE was performed on excised porcine lungs inflated with room air. Second, a phantom consisting of open-cell foam filled with thermally polarized (3)He gas was imaged with MRE to determine whether shear wave propagation can be encoded by the gas. Third, preliminary evidence of the feasibility of MRE in vivo was obtained by using a longitudinal driver on the chest of a normal volunteer to generate shear waves in the lung. The results suggest that MRE in combination with hyperpolarized noble gases is potentially useful for noninvasively assessing the regional elastic properties of lung parenchyma, and merits further investigation.     

Comparison of seizure detection algorithms in continuously monitored pediatric patients.

SUMMARY: Robust, automated seizure detection has long been an important goal in epilepsy research because of both the possibilities for portable intervention devices and the potential to provide prompter, more efficient treatment while in clinic. The authors present results on how well four seizure detection algorithms (based on principal eigenvalue [EI], total power, Kolmogorov entropy [KE], and correlation dimension) discriminated between ictal and interictal EEG and electrocorticoencephalography (ECoG) from four patients (aged 13 months to 21 years). Test data consisted of 46 to 78 hours of continuously acquired EEG/ECoG for each patient (245 hours total), and the detectors' accuracy was checked against seizures found by a board-certified neurologist and an experienced registered EEG technician. The results were patient-specific: no algorithm performed well on a 13-month-old patient, and no algorithm consistently performed best on the other three patients. One of the metrics (EI) supported the existence of a postictal period of 5 to 15 minutes in the three oldest patients, but no strong evidence of a preictal anticipation was found. Two metrics (EI and KE) cycled continuously with a period of several hours in a 21-year-old patient, highlighting the importance of continuous analysis to differentiate background cycling from anticipation.