Chemotherapy agents induce tartrate-resistant acid phosphatase 5a contributing to the symptom distress in lung cancer patients.

Tartrate-resistant acid phosphatase 5a (TRACP5a) is mainly secreted by activated macrophages in chronic inflammation. Serum TRACP5a is associated with symptom distress in lung cancer patients during chemotherapy. Therefore, this study aimed to investigate whether chemotherapy drugs modulate TRACP5a as an inducible marker for symptom distress in lung cancer patients during chemotherapy. In clinical analysis, lung cancer participants completely received the six-cycle chemotherapy process (n = 42). Clinical determinations for TRACP5a, C-reactive protein (CRP), interleukin-6 (IL-6), white blood cells, monocytes, and hemoglobin were analyzed at six time points: BL, C1d8, C2d1, C4d1, C4d8, and Ed28. Meanwhile, five questionnaires for fatigue, sleep disturbance, pain, depression, and confusion were finished before drug treatment. For monocyte-to-macrophage differentiation, THP-1 cells were treated with phorbol 12-myristate 13-acetate (PMA). TRACP5a secretion in THP-1 cells was determined at the following days up to 6 days after 1-day incubation of chemotherapy drugs by dot blotting. Clinical analysis revealed that TRACP5a significantly increased at C1d8 and C4d8, but dropped at C2d1 and Ed28. CRP and IL-6 displayed a broad-range variation, resulting in no significant difference among the assessment time points. In contrast, monocytes decreased at C1d8 and C4d8, but rose again at C2d1 and Ed28. In symptom distress, the changes only in fatigue and sleep disturbance were positively associated with the trend in TRACP5a. In PMA-treated THP-1 cells, TRACP5a significantly increased after stimulation with gemcitabine and paclitaxel. Taken together, induction of TRACP5a by chemotherapy drugs might be generated from monocyte-differentiated macrophages, further causing clinical symptom distress in lung cancer patients.

Self-reported confusion is related to global and regional ß-amyloid: data from the Women's healthy ageing project.

Disease-modifying treatments for Alzheimer's disease (AD) may require implementation during early stages of ß-amyloid accumulation, well before patients have objective cognitive decline. In this study we aimed to assess the clinical value of subjective cognitive impairment (SCI) by examining the cross-sectional relationship between ß-amyloid load and SCI. Cerebral ß-amyloid and SCI was assessed in a cohort of 112 cognitively normal subjects. Subjective cognition was evaluated using specific questions on memory and cognition and the MAC-Q. Participants had cerebral ß-amyloid load measured with 18F-Florbetaben Positron Emission Tomography (PET). No associations were found between measures of subjective memory impairment and cerebral ß-amyloid. However, by self-reported confusion was predictive of a higher global ß-amyloid burden (p = 0.002), after controlling for confounders. Regional analysis revealed significant associations of confusion with ß-amyloid in the prefrontal region (p = 0.004), posterior cingulate and precuneus cortices (p = 0.004) and the lateral temporal lobes (p = 0.001) after controlling for confounders. An in vivo biomarker for AD pathology was associated with SCI by self-reported confusion on cross-sectional analysis. Whilst there has been a large body of research on SMC, our results indicate more research is needed to explore symptoms of confusion.

Paroxysmal Hypertension Induced by an Insulinoma.

Insulinoma is a rare, usually benign, pancreatic neuroendocrine tumor. The clinical features of an insulinoma are fasting hypoglycemia with neuroglycopenic symptoms including confusion and unusual behavior, while hypertension is usually not associated with the disease. We herein report a patient with insulinoma who manifested paroxysmal hypertension and neuroglycopenic symptoms. The possible etiology of hypertension induced by an insulinoma is catecholamine release in response to hypoglycemia, which may cause acute hypertension through activation of the sympatho-adrenal system. This case implies that sustained hyperinsulinemia due to insulinoma can be functionally linked to the induction of paroxysmal hypertension.

Circulating microparticles in neuropsychiatric systemic lupus erythematosus.

AIM: Phosphatidylserine-rich microparticles derived from endothelial cells, platelets and leukocytes have been implicated as surrogate markers of cellular activation in systemic lupus erythematosus (SLE). Because microparticles have also been associated with many primary neurologic diseases, this study investigated whether cellular-derived microparticles are also implicated in neuropsychiatric SLE (NPSLE). METHOD: Plasma microparticles were measured in 51 SLE patients and 22 age- and gender-matched controls. Acute NPSLE was defined as major NPSLE (acute stroke, transient ischemic attack, psychosis, isolated seizures, major cognitive disorder, or acute confusional state) and NPSLE disease activity was measured with the neurologic components of the SLE Disease Activity Index (Neuro-SLEDAI). RESULTS: Neuro-SLEDAI levels varied widely in SLE patients, consistent with variable NPSLE activity. When considering all patients with SLE, there was no difference in total microparticles relative to matched controls, 2158/µL (interquartile range [IQR] 1214-3463) versus 2782/µL (IQR 1586-2990; P = 0.57) nor differences in microparticles derived from either platelets (P = 0.40), monocytes (P = 0.15) or endothelial cells (P = 0.32). However, levels of circulating monocyte-derived microparticles significantly and independently correlated with NPSLE (r = -0.28; P = 0.045), corticosteroid dosage (r = -0.38; P = 0.006) and levels of circulating C5a (r = 0.54; P < 0.0001). Non-neurologic SLE disease activity was not associated with microparticles. CONCLUSION: Circulating cell-derived microparticles are reduced in active NPSLE, although the relative contribution of reduced microparticle production, increased consumption or intravascular sequestration, remain uncertain.

Specific patterns of weak (1 microTesla) transcerebral complex magnetic fields differentially affect depression, fatigue, and confusion in normal volunteers.

Normal young adults were exposed for 20 min once per week for a total of 3 sessions to 1 of 7 configurations of weak (1 microTesla) magnetic fields or to a sham field. The fields were spatially rotated and applied through the brain at the level of the temporoparietal lobes. The Profile of Mood States was taken before and after each session. Before, during, and after the treatments, heart rate, plethysmographic activity, and skin conductance were measured by computer. The results indicated that the burst-firing pattern previously demonstrated to be effective for clinical depression, improved mood and vigour compared to the sham-field or other treatments. Subjects who were exposed to a burst-firing pattern, a complex-sequenced pattern, and a pattern whose electrical equivalents stimulate long-term potential in hippocampus slices also exhibited less psychometric fatigue after the sessions compared to subjects who received the sham field or random-sequenced fields. These results replicate previous studies and indicate that rationally designed complex patterns of magnetic fields may simulate pharmacological treatments.

Executive dysfunction in hyperhomocystinemia responds to homocysteine-lowering treatment.

An elevated serum homocysteine level is a risk factor for the development of cognitive impairment. Reported is a late-onset case of hyperhomocystinemia due to a vitamin B12 metabolic deficit (cobalamin C) with cognitive impairment, primarily in frontal/executive function. After homocysteine-lowering therapy, the patient's functional and neuropsychological status improved in conjunction with a decrease in leukoariosis on his MRI scan. These findings suggest that homocysteine-related cognitive impairment may be partially reversible.

Primer on clinical acid-base problem solving.

Acid-base problem solving has been an integral part of medical practice in recent generations. Diseases discovered in the last 30-plus years, for example, Bartter syndrome and Gitelman syndrome, D-lactic acidosis, and bulimia nervosa, can be diagnosed according to characteristic acid-base findings. Accuracy in acid-base problem solving is a direct result of a reproducible, systematic approach to arterial pH, partial pressure of carbon dioxide, bicarbonate concentration, and electrolytes. The 'Rules of Five' is one tool that enables clinicians to determine the cause of simple and complex disorders, even triple acid-base disturbances, with consistency. In addition, other electrolyte abnormalities that accompany acid-base disorders, such as hypokalemia, can be incorporated into algorithms that complement the Rules and contribute to efficient problem solving in a wide variety of diseases. Recently urine electrolytes have also assisted clinicians in further characterizing select disturbances. Acid-base patterns, in many ways, can serve as a 'common diagnostic pathway' shared by all subspecialties in medicine. From infectious disease (eg, lactic acidemia with highly active antiviral therapy therapy) through endocrinology (eg, Conn's syndrome, high urine chloride alkalemia) to the interface between primary care and psychiatry (eg, bulimia nervosa with multiple potential acid-base disturbances), acid-base problem solving is the key to unlocking otherwise unrelated diagnoses. Inasmuch as the Rules are clinical tools, they are applied throughout this monograph to diverse pathologic conditions typical in contemporary practice.

Survival with serum sodium level of 180 mEq/L: permanent disorientation to place and time.

A 41-year-old woman who had undergone transfrontal craniotomy for a pituitary tumor 4 months before presentation was admitted with confusion and orientation only to self. She had a fever of 40 degrees C. Serum sodium and chloride levels on admission were 180 and 139 mEq/L, respectively. Measured serum osmolality was 380 mOsmol/L with a urine osmolality of 360 mOsmol/L. Magnetic resonance imaging revealed a 1.5-cm mass in the sella turcica, which was nonfunctioning on endocrine evaluation. The "bright spot" of a normal posterior pituitary was absent. Central diabetes insipidus was confirmed by a 300% increase in urine osmolality with desmopressin. The patient survived her severe hypernatremia, which has 70% mortality with a serum sodium level of 160 mEq/L or above. However, she developed permanent (6 months) disorientation to time and place even when hypernatremia was corrected, which has not been described previously.

Acute confusional state following liver transplantation for alcoholic liver disease.

BACKGROUND: Neurologic complications occur in 10% to 20% of patients after liver transplantation. OBJECTIVE: To assess postoperative neurologic complications in relation to increased use of liver transplantation for alcoholic liver disease. METHODS: Neurologic complications in 40 patients who received liver transplantation for alcoholic liver disease were compared with those in 47 patients who had transplantation for hepatitis C. All patients were older than 50 years and received transplants between 1990 and 2000. RESULTS: Acute confusion for 3 or more days occurred in 48% of the patients with alcoholic liver disease but in only 6% of those with hepatitis C (p < 0.0001). Neurotoxicity related to calcineurin inhibitor medication occurred in 7% of the alcohol group and 15% of the hepatitis C group (p = 0.33). Critical illness polyneuropathy and myopathy were noted in 10% of the patients with alcoholism and 2% of the patients with hepatitis C (p = 0.18). A shorter duration of sobriety within the alcohol group was associated with acute confusional state (p = 0.02). An increased preoperative level of ammonia in serum was a risk factor for post-transplantation acute confusional state (p = 0.001). Patients with postoperative acute confusional state had a longer hospital stay (p = 0.0002). CONCLUSIONS: An acute confusional state occurred in more than half the patients with transplantation for alcoholic liver disease. Increased pretransplantation serum level of ammonia and shorter duration of sobriety were risk factors in these patients.

Diffuse metabolic abnormalities in reversible posterior leukoencephalopathy syndrome.

Two cases of reversible posterior leukoencephalopathy syndrome were examined with proton MR spectroscopic imaging. Widespread metabolic abnormalities, consisting of increased choline and creatine levels and mildly decreased N-acetylaspartate, occurred in regions with both normal and abnormal MR imaging appearances. In one case for which proton MR spectroscopic imaging follow-up was available, all metabolite levels had returned to normal by 2 months. Proton MR spectroscopic imaging may be helpful for the diagnosis and investigation of the underlying pathophysiology of reversible posterior leukoencephalopathy syndrome.