Radical-Generating Activity, Phagocytosis, and Mechanical Properties of Four Phenotypes of Human Macrophages.

Macrophages are the major players and orchestrators of inflammatory response. Expressed proteins and secreted cytokines have been well studied for two polar macrophage phenotypes-pro-inflammatory M1 and anti-inflammatory regenerative M2, but little is known about how the polarization modulates macrophage functions. In this study, we used biochemical and biophysical methods to compare the functional activity and mechanical properties of activated human macrophages differentiated from monocyte with GM-CSF (M0_GM) and M-CSF (M0_M) and polarized into M1 and M2 phenotypes, respectively. Unlike GM-CSF, which generates dormant cells with low activity, M-CSF confers functional activity on macrophages. M0_M and M2 macrophages had very similar functional characteristics-high reactive oxygen species (ROS) production level, and higher phagocytosis and survival compared to M1, while M1 macrophages showed the highest radical-generating activity but the lowest phagocytosis and survival among all phenotypes. All phenotypes decreased their height upon activation, but only M1 and M2 cells increased in stiffness, which can indicate a decrease in the migration ability of these cells and changes in their interactions with other cells. Our results demonstrated that while mechanical properties differ between M0 and polarized cells, all four phenotypes of monocyte-derived macrophages differ in their functional activities, namely in cytokine secretion, ROS production, and phagocytosis. Within the broad continuum of human macrophages obtained in experimental models and existing in vivo, there is a diversity of phenotypes with varying combinations of both markers and functional activities.

Redox-Activation of Neutrophils Induced by Pericardium Scaffolds.

Implantation of scaffolds causes a local inflammatory response whereby the early recruitment of neutrophils is of great importance not only for fighting the infection, but also for facilitating effective regeneration. We used luminol-dependent chemiluminescence, flow cytometry, ELISA, and confocal microscopy to assess the responses of neutrophils after the exposure to the scaffold-decellularized bovine pericardium (collagen type I) crosslinked with genipin (DBPG). We demonstrated that DBPG activated neutrophils in whole blood causing respiratory burst, myeloperoxidase (MPO) secretion, and formation of neutrophil extracellular trap-like structures (NETs). In addition, we studied platelets, another important player of the immediate immune host response. We found that platelets triggered redox-activation of isolated neutrophils by the pericardium scaffold, and likely participate in the NETs formation. Free radicals generated by neutrophils and hypochlorous acid produced by MPO are potent oxidizing agents which can oxidatively degrade biological structures. Understanding the mechanisms and consequences of redox activation of neutrophils by pericardium scaffolds is important for the development of new approaches to increase the efficiency of tissue regeneration.

Histopathological Changes of the Thyroid and Parathyroid Glands in HIV-Infected Patients.

Objective. To study histopathology of the thyroid and parathyroid glands in HIV-infected African Americans in the United States. Methods. A retrospective review of 102 autopsy cases done by the Department of Pathology at Howard University Hospital from 1980 through 2007 was conducted. The histopathological findings of the thyroid and parathyroid glands were reviewed, both macroscopically and microscopically. A control group of autopsy patients with chronic non-HIV diseases was examined. Results. There were 71 males (70%) and 31 females (30%) with an average age of 38 years (range: 20-71 y). Thirteen patients with abnormal thyroid findings were identified. Interstitial fibrosis was the most common histological finding (4.9%), followed by thyroid hyperplasia (1.9%). Infectious disease affecting the thyroid gland was limited to 2.9% and consisted of mycobacterium tuberculosis, Cryptococcus neoformans, and cytomegalovirus. Kaposi sarcoma of the thyroid gland was present in only one case (0.9%). Parathyroid hyperplasia was the most common histological change noted in the parathyroid glands. Comparing the histological findings of cases and controls, we found a similar involvement of the thyroid, with a greater prevalence of parathyroid hyperplasia in HIV patients. Conclusion. Thyroid and parathyroid abnormalities are uncommon findings in the HIV-infected African American population.

Solid-pseudopapillary carcinoma: a case study and literature review.

Solid-pseudopapillary tumour (SPT) is a rare exocrine tumour of the pancreas and is considered to have low malignant potential. Few morphological criteria are used to predict malignant behaviour such as equivocal perineural invasion, angioinvasion and invasion to surrounding tissue, and should be designated as solid-pseudopapillary carcinoma (SPC). We report a case of SPC. Clinical and radiological findings are typical for SPT with no metastatic disease. There is no tumour recurrence after 4 months postresection. Clinical history and radiological findings were retrieved from the patient's record sheet and Viarad system. H&E staining and few immunoproxidase staining were reviewed by several pathologists. The histological findings are typical for SPT, with additional perineural invasion. There is no angioinvasion or capsular invasion identified. This is our first experience in diagnosing and managing SPC. We look forward to seeing the patient's disease status during her next routine follow-up. We expect good disease-free survival and very low risk of tumour recurrence, in view of only one risk factor (perineural invasion) and uninvolved surgical margins by the tumour.

Diagnosis of follicular neoplasm in thyroid nodules by fine needle aspiration cytology: does the result, benign vs. suspicious for a malignant process, in these nodules make a difference?

OBJECTIVE: To address the likelihood of thyroid malignancy for each cytologic interpretation, highly cellular and benign vs. follicular carcinoma, with particular attention to the indeterminate cytologic result, follicular neoplasm. STUDY DESIGN: We retrospectively reviewed thyroid nodule cytologic and histologic interpretations from 1994 to 2002 in a tertiary medical center setting. Patients were referred for evaluation of thyroid nodules found incidentally or on physical examination. RESULTS: A total of 886 thyroid nodules were aspirated in 802 patients (500 benign, 195 indeterminate, 129 inadequate, 62 malignant). Of 195 indeterminate lesions, 180 were classified as follicular neoplasm or "cannot rule out/possible" follicular neoplasm, with 144 of these ultimately removed and with malignant histologic findings in 28. Any mention of follicular neoplasm in the cytology report conferred a 19.4% risk of malignancy in patients who went on to surgery (including an unexpected 18.2% rate of malignancy in the subcategory in which a possible follicular neoplasm was a secondary listing in an otherwise-benign cytologic differential diagnosis). CONCLUSION: There was no difference in the likelihood of histologic malignancy between the cytologic subcategories of "definite "follicular neoplasm and "cannot rule out/possible" follicular neoplasm. We recommend that cytologic reports on fine needle aspiration of thyroid nodules with a diagnosis of follicular neoplasm reflect this fact.

Palpation thyroiditis causing new-onset atrial fibrillation.

OBJECTIVE: Surgery-induced thyroiditis can pose a significant clinical problem that is underappreciated. We present a case of new-onset atrial fibrillation as a consequence of palpation thyroiditis in a 70-year-old man who underwent radical right neck dissection for malignant melanoma and review the limited literature on this topic. DESIGN: Biochemical parameters including thyrotropin, free thyroxine, triiodothyronine, erythrocyte sedimentation rate, C-reactive protein, thyroglobulin, thyroid stimulating immunoglobulins, thyroid binding inhibitory immunoglobulins, thyroid peroxidase, thyroglobulin antibodies, and 24-hour urine iodine were measured. Thyroid ultrasound and technetium-99m pertechnetate scintigraphy with radioactive iodine 131 uptake were employed for diagnostic purposes. MAIN OUTCOME: Following right neck exploratory dissection, the patient developed hyperthyroidism and atrial fibrillation. Imaging studies were compatible with right lobar thyroiditis. Other etiologies of thyroiditis were excluded. Despite normalization of thyroid function after 2 weeks, atrial fibrillation persisted and required cardioversion. CONCLUSIONS: Manipulation of the thyroid gland during neck exploratory surgery can result in hyperthyroidism with atrial fibrillation as a consequence. To avoid this complication, careful attention should be paid during surgical procedures or other clinical situations in which the thyroid gland is manipulated.

Catecholamine-induced cardiomyopathy.

OBJECTIVE: To review the pathogenesis as well as the clinical and laboratory features of catecholamine-induced cardiomyopathy associated with pheochromocytoma and other disorders and discuss the various treatment options available. METHODS: Materials used for this article were identified through MEDLINE, PubMed, and Google Scholar searches of the relevant literature from 1955 to the present. RESULTS: Catecholamines and their oxidation products cause a direct toxic effect on the myocardium. Catecholamines also exert a receptor-mediated effect on the myocardium. Catecholamine-mediated myocardial stunning has been implicated in the pathogenesis of stress-induced cardiomyopathy. Biopsy of the myocardium in patients with pheochromocytoma or those with stress-induced cardiomyopathy shows similar pathologic findings. The clinical features in pheochromocytoma-related cardiomyopathy include hypertension, dilated or hypertrophic cardiomyopathy, pulmonary edema due to cardiogenic and noncardiogenic factors, cardiac arrhythmias, and even cardiac arrest. Stress-related cardiomyopathy such as takotsubo cardiomyopathy occurs primarily in postmenopausal women. These patients may present with clinical features suggestive of an acute myocardial infarction or a hemodynamically compromised state. The definitive management of cardiomyopathy associated with pheochromocytoma includes medical treatment with alpha-adrenergic blockade, possibly along with angiotensin converting enzyme blockers and beta1-adrenergic receptor blockers, followed by excision of the tumor. Stress-induced cardiomyopathy is usually self-limiting; patients may require support with nonadrenergic inotropes. CONCLUSION: Recognition of catecholamine-induced cardiomyopathy, especially in patients with pheochromocytoma, before surgical treatment is important to minimize morbidity and mortality.

Removal of catechol from aqueous solutions by adsorption onto organophilic-bentonite.

Organophilic-bentonite, produced by exchange of cetyltrimethylammonium cation for metal cations on the bentonite, was exploited as adsorbent for removal of catechol from aqueous solutions using batch technique. The dependence of removal on various physico-chemical parameters, such as contact time (1-250 min), concentration (0.8-15.3 mmol L(-1)), temperature (30, 40, 50+/-1 degrees C) and pH (5-12) of the adsorptive solution were investigated. Obtained results show that catechol could be removed efficiently ( approximately 100%) at pH values > or =9.9. The uptake process follows first-order rate kinetics and the equilibrium data fit well into the Langmuir and Freundlich adsorption isotherms over a wide range of concentration (1-10 mmol L(-1)). The magnitude of change of free energy (DeltaG degrees ), enthalpy (DeltaH degrees ) and entropy (DeltaS degrees ) were determined.

Plasma glucagon levels suppressed by a glucose load in a man with incidental pancreatic glucagonoma.

OBJECTIVE: To describe a patient with a histologically proven pancreatic glucagonoma, noted incidentally during a follow-up visit for high aminotransferase levels, and to evaluate its autonomy with a standard 75-g oral glucose tolerance test. METHODS: We present the results of a 2-hour oral glucose tolerance test, with plasma glucagon and blood glucose levels measured every 30 minutes after an oral glucose load. In addition, we provide a brief review of the literature on the diagnosis and management of glucagonomas and the importance of long-term surveillance. RESULTS: In our patient, who had a 1-year history of impaired fasting glucose, plasma glucagon levels were persistently suppressed to within the normal range after oral glucose challenge. Octreotide scintigraphy revealed abnormal uptake in the pancreatic tail, and a 2.8-cm mass was removed at laparoscopic distal pancreatectomy. Immunohistochemical staining of the tumor tissue showed intense reactivity for glucagon. Plasma glucagon levels were reduced to <50 pg/mL postoperatively, and scintigraphic study at 4-month follow-up showed no residual uptake at the previous tumor site or elsewhere. CONCLUSION: Glucagon-secreting pancreatic tumors are extremely rare. A substantially elevated plasma level of glucagon is usually seen in patients with metastatic tumors. In the early stage of a glucagonoma, however, the plasma glucagon level may be only modestly elevated and may still be susceptible to normal negative feedback inhibition. We demonstrated plasma glucagon complete suppressibility after oral glucose challenge in a patient with a glucagonoma, the first such report in the literature.

Hypocholesterolemic and hepatoprotective effects of flaxseed chutney: Evidence from animal studies.

Rats fed with hypercholesterolemic diet showed a significant increase in serum total-cholesterol, liver homogenate total-cholesterol, HDL-cholesterol and changed LDL-cholesterol, and HDL/LDL ratio in comparison to control. Flaxseedchutney (FC) supplemented diet (15%, w/w) was found to be more effective in restoring lipid profile changes in rats fed with cholesterol, (1.0%). The activities of serum marker enzymes glutamate oxaloacetate transminase (GOT), glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) were elevated significantly in carbon tetrachloride induced rats. Administration of flaxseedchutney (15%, w/w) resulted in depletion of serum marker enzymes and exhibited recoupment thus showing significant hepatoprotective effect. It was observed that flaxseedchutney supplemented diet could lower the serum cholesterol and as a potential source of antioxidants it could exert protection against hepatotoxic damage induced by carbon tetrachloride (CCl(4)) in rats.

Effects of flaxseed(Linum usitatissimum) chutney on gamma-glutamyl transpeptidase and micronuclei profile in azoxymethane treated rats.

Antioxidant property of flaxseed chutney was evident by decreasing lipid peroxidation (TBARS) and predictor enzyme γ-glutamyl transpeptidase profile and micronuclei formation in azoxymethane treated rats. After 10 weeks, rats fed with either fiber-free basal diet or Antioxidant diet exhibited over sevenfold increase in γ-glutamyl transpeptidase activity and nearly fourfold increase in micronuclei load in comparison to controls (p<0.001). A significant reduction in both γ-glutamyl transpeptidase level (52%) and micronuclei formation (47%) was observed in fiber-free basal diet/Antioxidant diet/flaxseed chutney diet fed rats. Relative to rats fed fiber-free basal diet, the profile of γ-glutamyl transpeptidase and micronuclei load was not significantly altered.

Littoral cell angioma presenting as metastatic thyroid carcinoma to the spleen.

Papillary thyroid carcinoma (PTC) commonly metastasizes to cervical lymph nodes. Distant metastases are unusual with the lungs most frequently involved. Well-differentiated thyroid carcinoma very rarely presents with metastases to the spleen. This is the case of a 25-year-old man with a history of PTC (1.4 cm primary; no capsular invasion and negative lymph node metastases). One year after initial surgery, recurrent disease was found in multiple neck nodes by central neck dissection. Whole body scan (WBS) following a therapeutic ablation dose of 150 mCi I(131) revealed mediastinal metastases. Computerized axial tomography (CT) of the chest one year later showed no gross mediastinal or pulmonary disease. However, multiple large splenic lesions were incidentally noted. Evaluation by ultrasound (US) showed lesions to be solid echogenic masses without remarkable Doppler characteristics to suggest vascular tumors. US-guided percutaneous fine-needle aspiration biopsy (FNAB) of one lesion was nondiagnostic. After withdrawal from Levothyroxine, serum TSH was >100 mU/L with a thyroglobulin of 9.4 ng/mL and negative anti-thyroglobulin antibodies. Diagnostic WBS revealed faint splenic uptake but was otherwise unremarkable. Following treatment with 192 mCi I(131), WBS demonstrated increased activity in the mediastinum as well as in the spleen suggesting mediastinal and splenic metastases. Contrast CT of the abdomen showed multiple low-attenuated heterogeneously enhancing splenic masses, normal liver and no intra-abdominal lymphadenopathy. The largest mass (4.5 x 3.5 cm) was exophytic and in close proximity to the splenic capsule. Despite the serum thyroglobulin of only 9.4 ng/mL, the finding of I(131) accumulation within solid splenic masses led to a preoperative diagnosis of thyroid carcinoma metastases. To establish the diagnosis and to remove the risk for splenic rupture, a laparoscopic splenectomy was performed. Histopathologic analysis showed large littoral cell angiomas (LCA). False-positive radioiodine scintigraphy in the setting of PTC involving a vertebral hemangioma has been reported. To our knowledge, this is the first case that describes multiple angiomas mimicking metastatic thyroid carcinoma to the spleen. In one-third of all cases reported, LCA co-exists with various visceral organ cancers or malignant lymphoma. This is the first report of an association between LCA and thyroid carcinoma.

Bone mineral density and total body bone mineral content in 18- to 22-year-old women.

One hundred sixty-four (164) healthy, young Caucasian women enrolled as midshipmen at the United States Naval Academy with no known disease or bone injury were followed for 3.6 years. Change in bone mineral density (BMD) of the hip, lumbar spine and distal tibia, and total body bone mineral content (TBMC) was measured by dual energy X-ray absorptiometry (DXA). Bone mineral density and TBMC of these women were measured within 2 months (60 +/- 4 days) of entering the Academy and annually. Over the study period, hip BMD increased 2.26% (P < 0.001), lumbar spine BMD increased 3.27% (P < 0.001) and distal tibia BMD increased 5.2% (P < 0.001). Total body bone mineral content showed a 5.25% (P < 0.001) increase during the study period. In this group of young women, gain in BMD and TBMC continued until age 22. These results suggest that bone mass may accrue in certain groups of women beyond age 22. The significance of this increase in bone mass during early adulthood on risk for osteoporotic fractures in later life and its impact on exercise-related bone injuries are unknown and warrant further examination.

Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a randomized controlled trial.

CONTEXT: Standard therapy for patients with primary hypothyroidism is replacement with synthetic thyroxine, which undergoes peripheral conversion to triiodothyronine, the active form of thyroid hormone. Within the lay population and in some medical communities, there is a perception that adding synthetic triiodothyronine, or liothyronine, to levothyroxine improves the symptoms of hypothyroidism despite insufficient evidence to support this practice. OBJECTIVE: To evaluate the benefits of treating primary hypothyroidism with levothyroxine plus liothyronine combination therapy vs levothyroxine monotherapy. DESIGN, SETTING, AND PATIENTS: Randomized, double-blind, placebo-controlled trial conducted from May 2000 to February 2002 at a military treatment facility that serves active duty and retired military personnel and their family members. The trial included a total of 46 patients aged 24 to 65 years with at least a 6-month history of treatment with levothyroxine for primary hypothyroidism. INTERVENTION: Patients received either their usual dose of levothyroxine (n = 23) or combination therapy (n = 23), in which their usual levothyroxine dose was reduced by 50 micro g/d and substituted with liothyronine, 7.5 micro g, taken twice daily for 4 months. MAIN OUTCOME MEASURES: Scores on a hypothyroid-specific health-related quality-of-life (HRQL) questionnaire, body weight, serum lipid levels, and 13 neuropsychological tests measured before and after treatment. RESULTS: Serum thyrotropin levels remained similar and within the normal range in both treatment groups from baseline to 4 months. Body weight and serum lipid levels did not change. The HRQL questionnaire scores improved significantly in both the control group (23%; P<.001) and the combination therapy group (12%; P =.02), but these changes were statistically similar (P =.54). In 12 of 13 neuropsychological tests, outcomes between groups were not significantly different; the 1 remaining test (Grooved Peg Board) showed better performance in the control group. CONCLUSION: Compared with levothyroxine alone, treatment of primary hypothyroidism with combination levothyroxine plus liothyronine demonstrated no beneficial changes in body weight, serum lipid levels, hypothyroid symptoms as measured by a HRQL questionnaire, and standard measures of cognitive performance.

Effects of prior neck radiation therapy on clinical features of primary hyperparathyroidism and associated thyroid tumors.

OBJECTIVE: To compare the clinical and biochemical features, bone densitometry data, and results of diagnostic imaging to localize parathyroid tumors in patients with radiation-associated hyperparathyroidism (R-HPT) and patients with HPT who had no history of radiation exposure (NR-HPT). METHODS: We performed a retrospective analysis of 34 patients with HPT who underwent evaluation and subsequent neck exploration between 1990 and 1995. We recorded and compared the symptoms, biochemical findings, bone densitometry data, results of diagnostic imaging, and pathologic findings in R-HPT and NR-HPT groups. RESULTS: The R-HPT group (8 men and 4 women)generally was older than the NR-HPT group (14 men and 8 women), but the age difference was not statistically significant. Patients in the R-HPT group had received radiotherapy (6.9 to 21.7 Gy) between 2 and 9 years of age for various diagnoses. Eight patients (67%) in the R-HPT group and 13 (59%) in the NR-HPT group had no symptoms of HPT. The rest of the patients in both groups had nonspecific symptoms, such as fatigue and dyspepsia. Four patients (18%) in the NR-HPT group had nephrolithiasis, and 3 (14%) had skeletal manifestations at initial assessment. Serum calcium, phosphorus, and parathyroid hormone levels and 24-hour urine calcium excretion were similar in both groups. Mean lumbar spine bone mineral density was lower in women in the R-HPT group than in those in the NR-HPT group, but the prevalence of osteoporosis did not differ significantly in the two study groups. Sestamibi scintigraphy accurately localized adenomas in both groups equally well (sensitivity >90%). In the R-HPT group, 11 patients had a single parathyroid adenoma and 1 had hyperplasia of all four parathyroid glands. In the NR-HPT group, 21 patients had a single parathyroid adenoma and 1 had parathyroid hyperplasia. In nine patients in the R-HPT group, ultrasonography showed thyroid nodules >1 cm. Pathologic examination of surgical specimens in the R-HPT group confirmed thyroid carcinoma in 11 patients ( 10 papillary and 1 follicular can-cer); no patient in the NR-HPT group had thyroid cancer. Six weeks after thyroidectomy, patients with thyroid can-cer received 1311 (mean dose, 145 mCi), five of whom needed additional 1311 treatments. CONCLUSION: Patients with a history of childhood neck irradiation who have HPT have a high likelihood of coexisting thyroid cancer. This observation may justify surgical exploration rather than vigilant follow-up in asymptomatic patients with primary HPT and coexisting thyroid nodules who have a history of radiation exposure.