Increased Bone Marrow Activity Research Articles

A Pain in the Neck: An Adolescent with Neck Pain.

A Pain in the Neck: An Adolescent with Neck Pain.

Amygdalar Metabolic Activity Independently Associates With Progression of Visceral Adiposity.

Epidemiologic data link psychological stress to adiposity. The underlying mechanisms remain uncertain. To test whether (i) higher activity of the amygdala, a neural center involved in the response to stress, associates with greater visceral adipose tissue (VAT) volumes and (ii) this association is mediated by increased bone marrow activity. Massachusetts General Hospital, Boston, Massachusetts. Two hundred forty-six patients without active oncologic, cardiovascular, or inflammatory disease who underwent clinical 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging were studied. VAT imaging was repeated ∼1 year later in 68 subjects. Metabolic activity of the amygdala (AmygA), hematopoietic tissue activity, and adiposity volumes were measured with validated methods. The relationship between AmygA and baseline and follow-up VAT. AmygA associated with baseline body mass index (standardized β = 0.15; P = 0.01), VAT (0.19; P = 0.002), and VAT/subcutaneous adipose tissue ratio (0.20; P = 0.002), all remaining significant after adjustment for age and sex. AmygA also associated with bone marrow activity (0.15; P = 0.01), which in turn associated with VAT (0.34; P < 0.001). Furthermore, path analysis showed that 48% of the relationship between AmygA and baseline VAT was mediated by increased bone marrow activity (P = 0.007). Moreover, AmygA associated with achieved VAT after 1 year (P = 0.02) after adjusting for age, sex, and baseline VAT. These results suggest a neurobiological pathway involving the amygdala and bone marrow linking psychosocial stress to adiposity in humans. Future studies should test whether targeting this mechanism attenuates adiposity and its complications.

An Atypical Presentation of Alcoholic Hepatitis

Significant alcohol consumption leads to a variety of alcoholic liver diseases ranging from alcoholic fatty liver disease to alcoholic cirrhosis. Alcoholic hepatitis carries a high risk of mortality; therefore, it is important to identify patients early to guide treatment and management. We discuss an atypical presentation of alcoholic hepatitis, with initial concern for lymphoproliferative disease. Our patient was a 28—year—old Cantonese—American man presenting with one month of abdominal pain, fevers, night sweats, and weight loss. His social history was not impressive for chronic alcohol use;he was a social drinker who drank 1 beer and 3 whisky shots every 4 months. Physical exam revealed tachycardia, abdominal tenderness, hepatosplenomegaly, and diffuse jaundice with no stigmata of chronic liver disease. Labs revealed leukocytosis with white blood cell count of 22x103/uL, conjugated hyperbilirubinemia (total bilirubin:4.4mg/dL), elevated alkaline phosphatase(183 U/L), and an INR of 1.43. An infectious process was ruled out when cultures and CXR were unrevealing. An abdominal ultrasound revealed hepatomegaly and ascites, but no ductal dilatation,which was confirmed on MRCP. Given his age, presence of B symptoms, and lack of significant alcohol history, there was concern for underlying malignancy. A CT abdomen showed abdominal lymphadenopathy and hepatosplenomegaly with a subsequent PET—CT scan showing diffuse lymphadenopathy and increased bone marrow activity. Hematology performed a bone marrow biopsy that revealed no signs of a neoplastic process. Patient's bilirubin continued to rise to 20mg/dL so a transjugular liver biopsy was obtained. Measurements revealed portal hypertension with HVPG of 10 and histology demonstrated steatosis, mild portal fibrosis,and Mallory body formation with neutrophilic infiltrates, suggestive of alcoholic hepatitis. The patient's Maddrey Discriminant Function score was elevated at 34 and he was started on prednisolone. At day 7 his Lille score was 0.04, indicating response to steroids. He completed a 28—day course of prednisolone and had complete resolution of fevers, ascites and biochemical abnormalities, while remaining abstinent. This is a case of alcoholic hepatitis presenting atypically with B symptoms, lack of strong drinking history, and diffuse lymphadenopathy, all suggestive of lymphoma. This case highlights the importance of pursuing a liver biopsy early on to confirm a diagnosis of alcoholic hepatitis.

Amygdala Activity May Predict Future Cardiovascular Events

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessAmygdala Activity May Predict Future Cardiovascular EventsAaron LevinAaron LevinSearch for more papers by this authorPublished Online:20 Apr 2017https://doi.org/10.1176/appi.pn.2017.3b8AbstractResearchers find a biological link between effects of stress on the amygdala and later cardiovascular events.Higher emotional stress as measured by resting metabolic activity of the amygdala is associated with greater risk of subsequent cardiovascular disease events, according to a study published online January 11 in The Lancet. The findings “provide novel insights into the mechanism through which emotional stressors can lead to cardiovascular disease,” wrote researchers led by Ahmed Tawakol, M.D., an associate professor of medicine at Massachusetts General Hospital and Harvard Medical School.Tawakol and colleagues hypothesized that activity in the amygdala in response to stress increases arterial inflammation both directly and by way of activity in bone marrow.“What is novel here is the bridging of multiple areas of research,” said Peter Gianaros, Ph.D., a professor of psychology and psychiatry and director of the Behavioral Neurophysiology Lab at the University of Pittsburgh. Gianaros has also studied the relationship between the amygdala and cardiovascular disease but was not involved with Tawakol’s study.“It builds on threads of prior research that pointed in this direction and makes strong connections with research on the neurobiology of stress as well as with clinical cardiology,” said Gianaros. “Now we have the proof of concept and a vision of the future.”The amygdala is known to be a key component of the brain’s stress network. Past studies in mice suggested that amygdala activity in response to stress accelerates cytokine production and atherosclerosis, but whether the same was true of humans was unknown.Tawakol and colleagues examined data originally derived from cancer screening imaging studies of 293 patients. Using positron emission tomography/computed tomography (PET/CT) scans, they analyzed activity in the amygdala and in bone marrow, as well as arterial inflammation.During the median follow-up of 3.7 years, 22 patients experienced a cardiovascular disease event—including heart attacks, strokes, angina, or other events. Each increase of one standard deviation in resting amygdala activity predicted a 1.6 risk of a cardiovascular event. The results were significant even after adjusting for established cardiovascular risk factors.Greater amygdala activity was also associated with increased bone marrow activity, which the authors said led to increased arterial inflammation followed by cardiovascular disease events.“[T]he brain’s salience network, bone marrow, and arterial inflammation together form an axis that could accelerate the development of cardiovascular disease,” concluded Tawakol and colleagues. “Furthermore, our findings raise the possibility that efforts to attenuate psychosocial stress could produce benefits that extend beyond an improved sense of psychological well-being and could beneficially impact the atherosclerotic milieu.”Clinicians might eventually screen for and treat chronic stress just as they do for other cardiovascular risk factors, they suggested.Realistically, clinical applications are still well down the road, and much needs to be done to move the field forward, said Gianaros.“We’ll need to set norms and thresholds for amygdala activity and see cost reductions in the methods used to assess it,” he said. For instance, it would be helpful to know more about what factors contribute to elevated amygdala activity, how people vary in their appraisal of stressors, and whether the amygdala sensitizes individuals to stressors in the environment or if the increased activity is a result of repeated stressors, he said.“This rigorous study is a good example of how multidisciplinary work can lead to potential breakthroughs or make connections that don’t happen when working in silos,” said Gianaros. ■An abstract of “Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study” can be accessed here. ISSUES NewArchived

Increased Bone Marrow Activity on F-18-FDG PET/CT in Granulocyte Colony Stimulating Factor Producing Anaplastic Thyroid Carcinoma

A 57-year-old man presented with jugular swelling. A leukocytosis of 50,000 WBC/μL (95% neutrophils) was found. PET/CT demonstrated increased fluorine-18-fluorodeoxyglucose uptake in the cervical/retrosternal mass, in the bone marrow, and in the enlarged spleen. Bone marrow biopsy confirmed myeloid hypercellularity with a left shift, but there were no signs of dysplasia and no evidence of tumor infiltration. Pathology of the thyroidectomy specimen confirmed an anaplastic thyroid carcinoma. Serum granulocyte-colony stimulating factor was elevated to 38.8 pg/mL (normal range, <0.6 pg/mL); granulocyte/macrophage-colony stimulating factor was normal (<2 pg/mL).

Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin

Expression of hepcidin, the key hormone governing iron transport, is reduced by anemia in a manner which appears dependent on increased bone marrow activity. The temporal associations between plasma hepcidin and other iron parameters were examined in healthy humans after erythropoietin administration and venesection. Profound hepcidin suppression appeared abruptly 24 hours after subcutaneous erythropoietin (P=0.003), and was near maximal at onset, with peak (mid-afternoon) levels reduced by 73.2%, gradually recovering over the following two weeks. Minor changes in circulating iron, soluble transferrin receptor and growth differentiation factor-15 were observed after the reduction in hepcidin. Similar but more gradual changes in these parameters were observed after reducing hematocrit by removal of 250 mL blood. These human studies confirm the importance of a rapidly responsive marrow-hepcidin axis in regulating iron supply in vivo, and suggest that this axis is regulated by factors other than circulating iron, soluble transferrin receptor or growth differentiation factor-15.

Immature platelet fraction (IPF) in hospitalized patients with neutrophilia and suspected bacterial infection

Neutrophilia is frequently in hospitalized patients, so a screening test for infections would be very useful. The immature platelet fraction (IPF) is provided by the automated blood analyzer XE 2100 (Sysmex, Kobe, Japan) as a proportional value of the total optical platelet count [IPF%; an absolute count of immature platelets can also be obtained (AIPC)] to indicate the rate of platelet production. IPF could help to identify the aetiology of thrombocytopenia and to recognize the increased bone marrow activity as occurred during the course of infectious disease. We selected from daily routine cell blood counts 535 samples from adult patients (age >14 years) with neutrophilia (> 8 x 10(9)/L) and platelets > or =150 x 10(9)/L, to avoid bias due to physiological increase of IPF. In 153 patients blood cultures (BC) were done the same day of IPF determination because of clinically suspected infection (fever > or =38 degrees C). Eighty-nine samples (58.2%) had positive BC (75 Gram-positive agents, 14 Gram-negative). Using our IPF reference normal range [IPF% 2.39% (0.8-5.1); AIPC 5.15 x 10(9)/L (2-12.6)], we found a significantly (p<0.0001) higher level of IPF in samples with positive BC [mean IPF% 4.86+/-2.67%, median 3.8 (range 2.4-15.8); mean AIPC 14.74+/-9.26 x 10(9)/L, median 11.7, (range 4.7-44.9)] than in BC negative samples [mean IPF% 1.79+/-0.63%, median 1.7 (range 0.5-4.7); mean AIPC 6.55+/-3.58 x 10(9)/L, median 5.45 (range 1.6-20.4)]. The increased IPF shows a statistically significant correlation with BC positivity. This parameter could therefore be used in the daily laboratory routine in patients with neutrophilia as a low cost screening test for bacterial infection.

Red cell distribution width (RDW) changes in pregnancy

Objective: As part of an exercise in establishing normograms of hematological parameters in pregnancy, we studied the red cell distribution width (RDW) in healthy pregnant women. Methods: A longitudinal study of RDW measurements in 121 pregnant women at 16 and 34 weeks gestation and during labor and at Days 3 and 7 postpartum. All the women had uncomplicated pregnancies, minimum hemoglobin (Hb) of 11.0 g/dl at recruitment and took iron supplements from 16 weeks of gestation and until 7 days after delivery. All subjects went into spontaneous labor, 110 achieving a normal vaginal delivery while the remaining 11 were delivered by cesarean section. Two-way analysis of variance was used to study the changes in RDW between any given gestations to test the variability between and within subjects. Results: RDW increased significantly ( P<0.0001) between 34 weeks of gestation and the onset of labor. No significant changes occurred between 16 and 34 weeks gestation, or during the 7 days postpartum. Conclusion: This is the first longitudinal study analyzing the between and within women changes in RDW with progression of pregnancy. The unexpected rise in the RDW during the last 4–6 weeks leading up to the onset of labor suggests increased bone marrow activity. The stimulus is unknown, but as RDW changes are highly significant there may well be a useful indicator of impending parturition.

Erythropoietin life span in rats with hypoplastic and hyperplastic bone marrows

The metabolic fate of erythropoietin (EPO) remains unknown. Urinary excretion does not appear to play a major role and liver catabolism has been shown to occur only after terminal sugars on the hormone have been removed. However, it has been proposed that EPO is eliminated by consumption in the bone marrow. In order to examine the extent of such consumption we measured the half-life of radioidinated recombinant EPO injected intravenously (IV) to rats with bone marrows suppressed by cyclophosphamide or hypertransfusion and marrows stimulated by phenylhydrazine or bleeding. The mean half-life or erythropoietin in normal rats was 179 +/- 16 min, with similar half-lives found in the other rats regardless of decreased or increased bone marrow activity. The results indicate that it is unlikely that erythroid activity determines EPO life span and catabolism.

Liver-Spleen Imaging in Patients with Subacute Hepatic Necrosis and Chronic Hepatitis

Tc-99m-sulfur colloid reticuloendothelial images and percutaneous liver biopsies are correlated in 54 patients who presented with signs and symptoms of subacute hepatic necrosis or chronic active hepatitis. The scored Tc-99m-sulfur colloid scan is compared to the histological severity of disease. Serial scans and biopsies are compared. In patients with significant hepatocellular disease, the liver-spleen scan did not correlate well with the histological severity of disease. Changes in the spleen-to-liver ratio are more common than those in the liver or increased bone marrow activity, and appear earlier. In serial studies, changes in the Tc-99m-sulfur colloid scans correlate weakly with changes in histology.

Experimental production of heinz bodies in the pig

Heinz bodies were produced in pigs given a single injection of hydroxylamine or acetyl-phenylhydrazine, but were not produced with nitrite. Heinz bodies were in 90–95% of erythrocytes by 2 hours after injection of hydroxylamine and in 95–100% of erythrocytes by 24 hours after administration of acetylphenylhydrazine. The percentage of affected erythrocytes gradually declined to 40–50% at necropsy on day 17. Anemia was not produced, nor were there clinical signs that could be attributed to the presence of Heinz bodies. There was histologic evidence of increased hemosiderosis in the spleen and of increased bone marrow activity.

Effects of phytohaemagglutinin on homograft rejection.

ALTHOUGH phytohaemagglutinin (PHA) has been widely-investigated in vitro, relatively little is known about its effects in vivo1. It has been used in humans with aplastic anaemia, who subsequently showed evidence of increased bone marrow activity in some cases2. Gamble3 found that intravenous injection of PHA in mice resulted in increases in the cellularity, the proportion of immature cells, and the weight of the spleen, which were most marked 3 days after administration. Calne et al.4 used combined PHA and azathioprine (‘Imuran’) therapy in an attempt to prolong the survival times of renal homotransplants in dogs. Intravenous PHA potentiated the immunosuppressive action of azathioprine and was thought to have some immunosuppressive activity when used alone.

THE EFFECTS OF EXPERIMENTAL PLETHORA ON BLOOD PRODUCTION

THE EFFECTS OF EXPERIMENTAL PLETHORA ON BLOOD PRODUCTION