Clonality and X-inactivation patterns in hematopoietic cell populations detected by the highly informative M27 beta DNA probe [see comments]

About 80% to 90% of females are informative for X- inactivation/methylation analysis with the probe M27 beta, which would therefore seem attractive in assessing clonality in hematologic cell populations. Eighteen acute lymphoid or myeloid leukemias, three chronic lymphocytic leukemias, and three chronic myelogenous leukemias as well as 12 malignant non-Hodgkin's lymphomas mostly showed extremely skewed clonal X inactivation (median allelic cleavage ratio [ACR] of unmethylated/inactive M27 beta alleles was 50, range 1 to 100) or hypermethylation of both alleles. Two lymphomas showed random M27 beta X inactivation but clonal antigen-receptor gene rearrangements. In normal peripheral blood leukocytes from 105 healthy females aged 2 to 96 years, the median ACR was 2 (range 1 to 100). Thus, it was significantly lower than in the leukemias (P = .0001, Mann-Whitney test), but extremely skewed patterns (ACR > 10.8, ie, > 80th percentile) were seen not only in the leukemias but also in 21/105 samples (20%) of normal leukocytes, and significantly more frequent in a population of elderly women (aged 75 to 96 years) compared with healthy children (aged 2 to 8 years) and younger women (aged 20 to 58 years) (P = .00125; chi 2 test). We conclude that in a population of cells derived from the hematopoietic system where clonality is uncertain, skewed M27 beta patterns are not reliable indicators for the presence of a clonal neoplastic disorder. The basis for severe X- inactivation skewing is unclear at present, but this finding raises interesting questions regarding the composition of the hematopoietic stem cell pool.     

Increased activity and sensitivity of mitochondrial respiratory enzymes to tumor necrosis factor alpha-mediated inhibition is associated with increased cytotoxicity in drug-resistant leukemic cell lines

The drug-resistant leukemic cell lines, CEM/VLB100 and K/DAU600, are more sensitive to tumor necrosis factor alpha (TNFalpha)-mediated cytotoxicity compared with their parental cell lines, CCRF-CEM and K562 cl.6. Drug-resistant leukemic cell lines have more active mitochondrial function, which is associated with a greater susceptibility to TNFalpha- induced respiratory inhibition. TNFalpha blocked electron transfer at three sites, NADH dehydrogenase (complex I), succinate dehydrogenase (complex II), and cytochrome c oxidase (complex IV). Respiratory rate and electron transport chain enzyme activities were significantly inhibited in the drug-resistant, TNF-sensitive cell lines. Respiratory inhibition preceded cell death by at least 5 to 8 hours. The respiratory failure was not compensated for by appropriate up- regulation of the glycolytic pathway. Increasing mitochondrial respiratory rate and enzyme activities by long-term culture with 2 mmol/L adenosine 5'-diphosphate (ADP) and Pi sensitized both drug- sensitive and drug-resistant cells to TNFalpha-induced cytolysis. Intramitochondrial free radicals generated by paraquat only had a limited and delayed effect on respiratory inhibition and cytolysis in comparison with the effect of TNFalpha. We conclude that TNFalpha- induced cytotoxicity in leukemic cells is, at least in part, mediated by inhibition of mitochondrial respiration. Free radical generation by TNFalpha may not directly lead to the observed inhibition of the mitochondrial electron transport and other mechanisms must be involved.     

Effects of recombinant human megakaryocyte growth and development factor on platelet activation

The c-Mpl receptor for thrombopoietin and its recombinant related protein, the megakaryocyte growth and development factor (MGDF), is also expressed on circulating platelets. In the present study we evaluated the effect of MGDF on platelet aggregation in platelet-rich plasma (PRP) and in whole blood. The results obtained indicate that MGDF by itself did not affect platelet aggregation. However, when added before other agonists such as adenosine diphosphates (ADP), epinephrine (EPI), and thrombin (THR), it rendered platelets more sensitive. This "priming" effect of MGDF was dependent on the dose and on the time of platelet preincubation, and it occurred both in PRP and in whole-blood platelet aggregation. MGDF also "primed" the release of adenosine triphosphates and the production of thromboxane B2 by platelets stimulated with ADP, EPI, and THR. When added 15 seconds after the preincubation of platelets with subthreshold concentrations of ADP, EPI, and THR, MGDF exhibited a synergism with these agonists. Moreover, we observed a "priming" effect of MGDF on the phosphorylation of p-42 mitogen-activated protein kinase promoted by ADP, EPI, and THR. These observations suggest that thrombopoietin may play a physiologic role in modulating the response of platelets to several stimuli and thereby their hemostatic potential.     

Chronic otomastoiditis: a conceptual understanding of CT findings

Inflammation of the middle ear cleft is a disease of great interest from both clinical and radiologic points of view. The attic floor (tympanic diaphragm), the tympanic isthmus, and the aditus ad antrum play important roles in inflammatory processes of the middle ear cleft. The anatomy of the temporal bone at this level was examined by studying microdissections of 250 fresh temporal bones and reviewing over 1,000 high-resolution computed tomography (CT) scans of the temporal bones. The pertinent anatomy is described, and the role of the tympanic diaphragm and isthmus in determining the degree to which middle ear disease may progress is stressed. The appearances on CT scans of chronic otomastoiditis, tympanosclerosis, cholesterol granuloma, attic retraction pocket, and acquired cholesteatoma are reviewed and illustrated.     

Occlusive and reperfused myocardial infarcts: differentiation with Mn- DPDP--enhanced MR imaging

To assess whether the administration of manganese N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid (DPDP) permits differentiation between occlusive and reperfused infarcts, the authors subjected rats to either 6 hours of left coronary artery occlusion (n = 13) or 2 hours of occlusion followed by 4 hours of reperfusion (n = 10) before magnetic resonance (MR) imaging. Electrocardiographic-gated T1-weighted images were obtained before and for 1 hour after injection of 400 mumol/kg of Mn-DPDP. On T1-weighted images obtained before injection of Mn-DPDP. no significant differences in signal intensity were observed between normal and infarcted regions. Use of Mn-DPDP permitted delineation of the area of infarction. The pattern of enhancement in the injured zone was different for occlusive and reperfused myocardial infarcts. In rats with occlusive infarcts, In rats with occlusive infarcts, three well-defined zones were seen. Epicardium and endocardium were enhanced, while the midmyocardial zone was hypointense. The midmyocardial signal intensity gradually increased during the 60 minutes after injection. In rats with reperfused infarcts, the injured area was uniformly and intensely enhanced. Histologic examination confirmed the presence and location of myocardial infarct. Mn-DPDP may improve the detection and delineation of acute myocardial infarcts, demonstrate perfusion of the infarct, and permit discrimination between reperfused and occlusive infarcts.     

Sex cord tumour of the adult testis

Sex cord stromal tumors are rare and account for approximately 6% of all testicular neoplasms. We report a case of sex cord tumor composed of granulosa cells and Sertoli cells in the adult testis.     

Pulmonary sarcoidosis in the older patient: conventional radiographic features

The clinical and radiographic findings in 29 patients presenting with pulmonary sarcoidosis after the age of 50 years were reviewed. Fifty-nine percent (17 patients) had atypical findings at presentation. The atypical patterns at radiography included mediastinal adenopathy alone or in combination with unilateral hilar adenopathy (n = 8), solitary or multiple pulmonary masses (n = 3), and atelectasis (n = 3). Five patients had extrathoracic tumors at the time that the diagnosis of pulmonary sarcoidosis was made, which confused the diagnosis at radiography. An enhanced awareness of the atypical patterns of sarcoidosis in the older patient may facilitate the diagnostic process.     

Microvascular anastomosis with minimal suture and Arista: an experimental study

BACKGROUND: The conventional technique of microvascular anastomosis may cause trauma to the vessel wall. In addition, the technique is difficult for beginners and is time consuming. The duration of ischemia is an important limiting factor for muscle transfer. In the case of multiple-digit replantations, fatigue developed in the surgeon may also result in suboptimal results. This study was performed to establish an easier and shorter method of microvascular anastomosis using the Arista hemostatic agent. METHODS: In this study, 20 carotid arteries obtained from rats were equally divided into two groups. The arteries were then divided and repaired using three simple interrupted stay sutures with Arista powder. Evaluations were performed using the following three methods: (1) clamping time during the vessel anastomosis, (2) patency test (after 1 hour, 24 hours, and 28 days), and (3) light microscopic findings. RESULTS: The clamping time in the conventional suture anastomosis group was 21+/-4 minutes, whereas that of the minimal suture in the Arista group was 12+/-2 minutes; the difference between the two groups was statistically significant (P<.001). There was no significant difference between the patency rates of the two groups (P= .474). It was observed that the Arista group showed qualitatively less perivascular foreign-body giant cell reaction than the control group. There was no evidence of vascular mural fibrinoid necrosis, indicating that Arista was nontoxic for the vessel walls. CONCLUSIONS: The Arista-assisted microvascular anastomosis is an alternative to the conventional suture-only method because it reduces the anastomosis time significantly and does not cause narrowing of the vessel wall. We believe that this technique has the potential for improving the performance of microvascular anastomosis in clinical practice.     

Is sildenafil citrate an alternative agent in the evaluation of penile vascular system with color Doppler ultrasound?

IINTRODUCION: The ideal diagnosis and therapeutic agent for erectile dysfunction (ED) would be an oral drug taken prior to color Doppler ultrasound (CDU) examination and sexual intercourse. In the present study we have investigated if the efficacy of oral sildenafil is optimal in the diagnosis of underlying pathology of ED. MATERIAL AND METHODS: The study group comprised of 41 patients with ED. Firstly, all patients underwent CDU examinations after the combined intracavernosal injection of 60 mg of papaverine and sexual stimulation (CIS). Secondly, these patients were examined after taking 50 mg of oral sildenafil citrate combined with self-manual and visual sexual stimulation. RERSULTS The differences of peak systolic velocity values were statistically significant between CIS and sildenafil (right: 40.7 +/- 2.9 vs. 28.7 +/- 3.3; left: 41.2 +/- 3.3 vs. 25.7 +/- 2.4; p < 0.001) in patients with normal penile vascular system. However, end-diastolic velocity and resistance index values were not significant between the same groups. In addition, there were not significant differences for peak systolic and end-diastolic blood flow velocities and resistances index with CIS and sildenafil in cases with vasculogenic ED. CONCLUSIONS: Sildenafil citrate plus visual sexual stimulation is not reliable as CIS to make accurate interpretation of penile vascular status using CDU. On the other hand, in some cases suspected of psychogenic ED after detailed sexual history, sildenafil might be tried as an initial step of the functional evaluation with CDU in order to prevent prolonged erection risk with intracavernosal injection of vasoactive agents.     

Evaluation of penile hemodynamic status and adjustment of treatment alternatives in Peyronis‘s disease

Aim:Erectile dysfunction may be observed in up to 80%of patients with Peyronis‘s disease.An objective evaluation of the erectile function is attempted to work out in patients with Peyronie‘s disease.Methods:Penile deformity,sexual function and penile vascular status were analyzed in 123patients with Peyronis‘s disease,who had not received any pertinent treatment.Results:Penile edformity,palpable plaque and pain on erection were seen in112(91%),97(78.8%)and27(21.9%)of the123patients,respectively.Of the 76patients evaluated by color Doppler ultrasounography,veno-occlusive dysfunction as the vascular component for erectile dysfunction was found in 17(22.3%),arterial insufficiency in10(13.1%)and a mixed picture in 23(30.2%).Conclusion:The documentation of penile erectile function and the determination of the vascular status using color Doppler ultrasonography can guide the appropriate therapeutic choice.