Implementation of flow cytometry in the diagnostic work-up of myelodysplastic syndromes in a multicenter approach: report from the Dutch Working Party on Flow Cytometry in MDS

Flow cytometry (FC) is recognized as an important tool in the diagnosis of myelodysplastic syndromes (MDS) especially when standard criteria fail. A working group within the Dutch Society of Cytometry aimed to implement FC in the diagnostic work-up of MDS. Hereto, guidelines for data acquisition, analysis and interpretation were formulated. Based on discussions on analyses of list mode data files and fresh MDS bone marrow samples and recent literature, the guidelines were modified. Over the years (2005-2011), the concordance between the participating centers increased indicating that the proposed guidelines contributed to a more objective, standardized FC analysis, thereby ratifying the implementation of FC in MDS.     

Soluble P selectin levels in chronic liver disease: relationship to disease severity

BACKGROUND/AIMS: Thrombocytopenia and platelet function abnormalities are problems commonly found in patients with chronic liver disease (CLD). Despite lack of widespread recognition as to the clinical significance of Soluble P-selectin (sP-selectin), in that increased levels of sP-selectin have been described in patients with CLD, it has been proposed as a marker of in-vivo platelet activation. The study's aim was to determine whether levels of sP-selectin in patients with CLD increase in accordance with the degree of liver failure, the likelihood of CLD patients with high sP-selectin levels being more prone to thrombosis, as well as investigating the coagulation and fibrinolytic parameters related to the sP-selectin. METHODOLOGY: This study was comprised of two groups: 40 patients with cirrhosis and portal hypertension (28 males and 12 females); and a control group of 10 healthy volunteers (6 males and 4 females). In both groups, biochemical parameters, sP-selectin, coagulation and fibrinolytic activity levels were measured and a Doppler ultrasound was performed. RESULTS: Plasma sP-selectin levels were found to be higher in the patients compared to those of the control group (p < 0.01), while at the same time significant differences were observed with respect to the stage of disease. Patients with low platelet counts were found to have higher sP-selectin levels than those with normal platelet counts (p < 0.01). Seven patients (17.5%) were seen to have portal vein thrombosis upon doppler ultrasound examination, while sP-selectin levels were significantly lower in those patients with thrombosis than those without (p < 0.05). It was our finding that sP-selectin levels inversely correlated with anti thrombin III. CONCLUSIONS: In conclusion, sP-selectin levels related to the degree of liver disease and thrombosis are seen together with low platelet and sP-selectin levels in patients with cirrhosis.     

Effect of pinealectomy on the morphology of the chick cervical spinal cord: a stereological and histopathological study

Melatonin has some effects upon morphological features of various structures in small animals and human being. In this study, the changes induced by pinealectomy procedure on morphological features of developing cervical spinal cord and their neurons in the gray matter (GM) and white matter (WM) of cervical spinal cord in the chicken were investigated. A total of 15 Hybro Broiler newly hatched chicks were randomly divided into three equal groups: unoperated control group (n=5), sham-operated group (n=5) and pinealectomy group (n=5). Pinealectomy procedure and sham operation were done in 3-day-old chicks and all animals were sacrificed at the 8th week and the 6th cervical (C6) spinal cord segment was dissected out for histopathological evaluation and subsequent stereological analysis. The volume of spinal cord segment did not show a significant difference between unoperated and sham-operated controls, but the pinealectomy group has a declined volume value compared with those of the control and sham operated groups (P<0.01). By contrast, there was no statistically significant difference between unoperated and sham-operated controls and the pinealectomy group with regard to volume fraction of the GM and WM of the cervical spinal cord. Finally, it was observed that pinealectomy procedure significantly reduces neuron number in the GM and the volume of WM of the C6 segment of cervical spinal cord in the chicken (P<0.001). The present study is the first study at all to evaluate the effects of pinealectomy on quantitative feature of the spinal cord in the chicken. Based on our findings, we suggest that pineal gland/melatonin might play an important role in morphological features of the developing spinal cord in the chicken.     

Primary neuroendocrine carcinoma of the breast: a case report

Primary neuroendocrine carcinoma of the breast is an extremely rare tumor. We present our experience of primary neuroendocrine carcinoma of the breast in a 76-year-old woman. Surgical biopsies from breast and axillary lymphadenopathy showed a neuroendocrine carcinoma. Immunohistochemical staining of tumor cells with GCDFP15, NSE and chromogranin were positive. Computed tomography scans of the chest and abdomen showed no lesion for metastasis or another primary origin. Adjuvant hormone therapy was given, since the tumor was immunohistochemically receptor positive.     

Synthesis and Antifungal Activity of 1‐Aryl‐3‐phenethylamino‐1‐propanone Hydrochlorides and 3‐Aroyl‐4‐aryl‐1‐phenethyl‐4‐piperidinols

Mono‐Mannich bases, 1‐aryl‐3‐phenethylamino‐1‐propanone hydrochlorides, 1a, 2a , 3a , 4a , 5a , 6a , 7a , 8a , 9a , and semi‐cyclic mono‐Mannich bases, 3‐aroyl‐4‐aryl‐1‐phenethyl‐4‐piperidinols, 1b , 2b , 3b , 4b , 5b , 6b , 7b , 8b , 9b , were synthesized by a non‐classical Mannich reaction. The aryl part was: C₆H₅ for 1a , 1b ; 4‐CH₃C₆H₄ for 2a , 2b ; 4‐CH₃OC₆H₄ for 3a , 3b ; 4‐ClC₆H₄ for 4a , 4b ; 4‐FC₆H₄ for 5a , 5b ; 4‐BrC₆H₄ for 6a , 6b ; 2,4‐(Cl)₂C₆H₃ for 7a , 7b ; 4‐NO₂C₆H₄ for 8a , 8b ; and C₄H₃S(2‐yl) i. e., 2‐thienyl for 9a , 9b . Piperidinol compounds 2b , 3b , 4b , 5b , 7b , 8b , and 9b are reported here for the first time. The synthesized compounds were tested against seven types of plant pathogenic fungi and three types of human pathogenic fungi using the agar dilution assay. Itraconazole was tested against Candida parapsilosis as the reference compound, while Nystatin was tested as the reference compound against the other fungi. Compounds 1a , 1b , 2a , 4a , 4b , 5a , 5b , 6a , 7a , 8a , 9a , and 9b can be selected as model compounds to develop new antifungal agents against the human pathogen Microsporum canis. Compounds 8a and 8b , which had a similar antifungal activity compared with the reference compound Nystatin against the plant pathogen Aspergillus flavus, can serve as model compounds to develop new antifungal agents to solve agricultural problems.     

Factors Predicting Outcome of Balloon Dilatation in Achalasia

Background Balloon dilatation of the lower esophageal sphincter (LES) is one of the effective nonsurgical treatment options in the management of achalasia. We aimed to determine the long-term results of graded balloon dilatation and the factors predicting outcome. Patients Patients followed for more than 12 months between January 1995 to March 2005, without history of endoscopic or surgical therapy before the study, were included (n = 111, mean age 46.3 ± 16.9 years; follow-up period 46.3 [12–150] months). Patients were evaluated by barium swallow contrast studies, upper endoscopy, and esophageal manometry. Pneumatic dilatation was performed with the use of polyethylene balloon system. Patient outcome was evaluated according to manometric studies and Van Trappen staging as determined following face-to-face interviews with the patients. Results We determined clinical response rates of 98%, 85.7%, and 75% at months 24, 48, and 60. According to receiver-operating characteristics (ROC) analysis, age ≤37.5 years, LES pressure (LESP) ≥30.5 mmHg, LESP after first balloon dilatation ≥17.5 mmHg, and balloon number >2 were found to negatively affect treatment response. Young age and higher esophageal body pressure at admission were determined to be negative predictive factors (P = 0.038, relative risk (RR) 2.6, 95% confidence interval [CI] 1.05–6.4 and P = 0.05, RR 1.069, 95% CI 0.99–1.14, respectively). Conclusion Balloon dilatation is an effective treatment of achalasia. Young age, higher esophageal body pressure, and high LESP after first balloon dilatation are negative predictive factors. Patients with young age requiring more than two balloon dilatations are likely to be unresponsive to the treatment.     

Second malignant neoplasms following the treatment of brain tumors in children

We investigated retrospectively 992 children with central nervous system tumors who were treated at our center between 1970 and 2004. All of the patients were treated by surgery, chemotherapy, and/or radiotherapy. Six patients developed second malignant neoplasms, and their clinical and histopathologic characteristics are reviewed in this article. The second malignant neoplasms were diagnosed as non-Hodgkin lymphoma, myelodysplastic syndrome, basal cell carcinoma, malignant melanoma, Kaposi sarcoma, and high-grade neuroectodermal tumor. The initial diagnoses were ependymoblastoma in one, medulloblastoma in three, and low-grade astrocytoma in two patients. The median latency time was 3.03 years (range 0.39-22.93 years). The outcome varied according to the histopathologic type of the second tumor. The patients who developed non-Hodgkin lymphoma and myelodysplastic syndrome died of progressive disease. The patients with second skin neoplasms are alive as of the time of this writing. The patient with Kaposi sarcoma developed one of the rare reported second malignant neoplasms following a primary brain tumor in childhood. A wide spectrum of second malignant neoplasms was detected after treatment of primary brain tumors with surgery, radiotherapy, and chemotherapy. Long-term follow-up is therefore necessary for the child who has survived a primary central nervous system tumor.     

Corticospinal tract involvement in a patient with 3-HMG coenzyme A lyase deficiency

3-Hydroxy-3-methylglutaryl coenzyme A lyase deficiency, an inborn error of ketone body synthesis and leucine degradation, is a rare disorder. There are few reports demonstrating clinical and neuroradiologic findings of this condition. This report describes a 3.5-year-old previously healthy male who was admitted with complex partial seizures and was diagnosed as having 3-hydroxy-3-methylglutaryl coenzyme A lyase deficiency. The patient's previous medical history was unremarkable. His development and neurologic examination were normal. Cranial magnetic resonance imaging indicated prominent corticospinal tract and pontine involvement with focal cerebral white matter changes which have not been described in the literature before.