Splenectomy: the last option of immunosuppressive therapy in patients with chronic or relapsing idiopathic thrombotic thrombocytopenic purpura?
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Biomedical subjects
Publications and source records attributed to M Modic.
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To improve our understanding of the regulation of circulating platelet counts (PC) by thrombopoietin (TPO), we studied serum TPO levels and PC before and after myelosuppressive chemotherapy in 12 patients with acute myeloid leukaemia (AML). Serum TPO levels were measured by the quantitative sandwich enzyme-linked immunosorbent assay (Quantikine, RD Systems). At the start of the induction chemotherapy, the patients had a median serum TPO level of 199 pg/ml (range 120-2,150 pg/ml), while 10 to 12 days after the end of chemotherapy, their TPO levels were substantially increased, the median value being 1,907 pg/ml (range 1,049-4,194 pg/ml). The correlation between PC and TPO was statistically significant prior to chemotherapy (p < 0.03) and insignificant after chemotherapy. As a result of chemotherapy, the patients developed aplasia; after the administration of platelet transfusions, their median PC increased to 21 x 10(9)/l (range 5-55 x 10(9)/l), while the median TPO value decreased by 300 pg/ml (range 11-1,125 pg/ml). Our results suggest that platelet mass directly regulates serum TPO levels in acute leukaemia patients prior to chemotherapy and after the administration of platelet transfusions. Serum TPO levels may also be influenced by the cytokine response during complicating infections in patients with chemotherapy-induced cytopenia.
Iron deficiency in patients with end stage renal disease (ESRD) treated by haemodialysis (HD) is difficult to diagnose. The reticulocyte hemoglobin content (CHr) and the percentage of hypochromic red cells (%hypo) are sensitive novel assays for the detection of functional iron deficiency in patients treated with erithropoietin (EPO). In our study thirty-nine chronically hemodialyzed patients were evaluated to determine the value of these two parameters in comparison to the conventional biochemical indicators of iron metabolism. There were significant correlations between CHr and transferrin saturation, CHr and weekly dosage of EPO, and also between %hypo and weekly dosage of EPO. Our data represent superior value of %hypo and CHr to the transferrin saturation and ferritin concentration in detecteng of iron deficiency in HD patients.
Myelokathexis is a very rare form of chronic hereditary neutropenia resulting from impaired neutrophil releasing mechanism in the bone marrow. The recombinant human granulocyte-macrophage (molgramostim) and granulocyte (filgrastim, lenograstim) colony stimulating factors release the mature granulocytes from the bone marrow. We describe a 43-year-old woman suffering from myelokathexis, with the absolute neutrophil count ranging between 0.03 and 1.35 x 10(9)/L. In the period before the introduction of cytokines, the patient had more than 80 major infectious episodes. Since 1991, infections in this patient have been treated with cytokines, given in conjunction with antibiotics. Initially, she received molgramostim in a daily dose of 5 microg/kg subcutaneously, which stimulated the release of granulocytes from her bone marrow, thereby allowing successful treatment of infection. After the development of hypersensitivity, molgramostim was substituted with filgrastim. Finally, lenograstim was given a trial. With all three cytokines, the patient's neutrophil count always attained normal values already 4 hours after subcutaneous application of the drug in a dose of 5 microg/kg, the highest neutrophil levels were measured at 24 hours post-injection, and the neutrophil count was again close to the baseline value 72 hours after the treatment. A slight neutropenia was present 48 hours after the application of filgrastim. We believe that all three cytokines are equally effective in increasing the neutrophil count in venous blood of patients with myelokathexis.
Precise localization of the epileptogenic zone in patients suffering from mesial temporal lobe epilepsies is a prerequisite for surgery. For this purpose, a scheme for selecting the volume of interest in an oblique plane covering the head, body, and tail of the hippocampal formation (HF) was implemented in a water-suppressed proton chemical shift imaging (CSI) acquisition. This approach, evaluated by consecutively acquired CSI spectra of both temporal lobes, demonstrates that it can potentially be a routine technique for clinical diagnosis. Since the method produces localized spectral detail of the HF, it facilitates a convenient comparison of CSI lateralization to that assessed by HF atrophy (due to sclerosis) using the MRI-volumetry technique.
PURPOSE: We studied temporal changes of brain sodium and apparent diffusion coefficient (ADC) in a temporal lobe epilepsy (TLE) rat model using kainic acid (KA). METHODS: In situ three-dimensional 23Na magnetic resonance imaging (MRI) and proton diffusion-weighted imaging (DWI) were used. KA at a dose of 10 mg/kg body weight and 12 adult Sprague Dawley rats weighing 228-318 g (268 +/- 25 g) were used. RESULTS: Twenty-four hours after KA injection, magnetic resonance (MR) visible sodium levels increased in both the pyriform cortex (+90%) and amygdala (+68%) and increased insignificantly in the hippocampus (+18%) and caudate-putamen (12%). The ADC in the pyriform cortex showed a -9% decrease at 5 h postictally, reaching -30% at 24 h, whereas in the amygdala decreases were -8 and -26% respectively. A significant decrease in ADC (-7%) in the hippocampus was also observed 24 h postically. Seven days later, sodium increases persisted, whereas ADC returned to normal level. CONCLUSIONS: The increase in MR visible sodium, associated with the decrease in ADC is consistent with the hypothesis that sequential seizures caused an increase in sodium influx and perturbation of membrane ion homeostasis, which eventually evolved into an irreversible phase of cellular edema, with increased MR visible intracellular sodium and decreased ADC. Return of ADC to near-control level and persistent high sodium level at 7 days may be explained by the increase in extracellular space and tissue necrosis.
PURPOSE: To assess two-dimensional phase-encoded proton chemical shift imaging for potential clinical application in presurgical localization of temporal lobe epilepsy (TLE). MATERIALS AND METHODS: Interictal chemical shift imaging studies were performed in 25 patients (17 unilateral, eight bilateral epileptogenic abnormalities) and 12 healthy volunteers. Results were compared with those of electroencephalography. For each temporal lobe, the volume of interest (VOI) included mesial, lateral, anterior, and posterior areas. RESULTS: The epileptogenic zone was characterized by an abnormal pattern of decreased signal intensity in the N-acetylaspartate (NAA) peak, either increased or unchanged choline (Cho) level relative to creatine (Cr) signal intensity, and, occasionally, elevated lactate level. NAA/Cho was the most sensitive and reliable quantitative marker for abnormality. The sensitivity and specificity of this technique compared with EEG were 90% and 85%, respectively. The difference in NAA/Cho between epileptogenic and normal temporal lobes was highly significant (P < .001). No statistically significant difference was found between normal temporal lobes and patients' uninvolved temporal lobes. CONCLUSION: NAA/Cho is an excellent marker for localizing the epileptogenic zone in TLE.
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A patient with see-saw nystagmus had a lesion localized by Magnetic Resonance Imaging (MRI) to the paramedian ventral midbrain with involvement of the right interstitial nucleus of Cajal. This the first MRI study of see-saw nystagmus associated with a presumed brainstem vascular event. Our findings support animal and human studies suggesting that dysfunction of the interstitial nucleus of Cajal or its connections is central in this disorder.
Fifty consecutive patients treated with chymopapain injection for a clinical and radiographic diagnosis of herniated nucleus pulposus were evaluated prospectively. All patients had a prechymopapain computed tomography (CT) scan and a three-month postinjection CT scan. In addition, ten patients (20%) had a six-month postinjection CT scan. All scans were interpreted blindly. Only six patients (12%) had obvious changes in the size of the disc when preinjection and three-month postinjection CT scans were compared. By six months, however, seven of ten patients (70%) had obvious changes in their CT scan. Seven patients (14%) were considered chymopapain treatment failures and were later treated with surgical discectomy. Only two of these seven patients (30%) had obvious changes in their three-month CT scan. Chymopapain injection did not alter the size of the herniated portion of the disc during the first three months after chymopapain injection. A decision to operate for presumed chymopapain failure should therefore be based on clinical grounds, rather than on the three-month CT appearance of the herniated disc.
Preoperative intravenous digital subtraction angiography (IV DSA) was compared with the operative findings in 54 patients who underwent a total of 57 carotid endarterectomies, to evaluate the accuracy of preoperative IV DSA in predicting the lesion found at surgery. Four studies early in the series were technically unsatisfactory, leaving 50 patients with 53 procedures for evaluation. Severe carotid artery stenosis was accurately predicted in all cases. Deep ulceration in the absence of severe carotid stenosis was reliably shown by IV DSA, although it was not reliably demonstrated by either IV DSA or carotid angiography if severe stenosis was also present. As severe carotid stenosis or deep ulceration are the major radiological indications for carotid endarterectomy, the authors have found that technically satisfactory IV DSA is an adequate preoperative imaging technique.
A patient undergoing external carotid artery therapeutic embolization for obliteration of a dural arteriovenous malformation suddenly developed a large occipital artery to vertebral artery shunt. A devastating stroke was averted because the appearance of the shunt was observed by fluoroscopy, the embolization was stopped, and the shunt verified on a subsequent angiogram. The risk of external carotid artery embolization without constant fluoroscopic control is emphasized.
Twenty-two patients with the clinical diagnosis of transient ischemic attacks were prospectively evaluated by computed tomography (CT) and proton magnetic resonance imaging (MRI). Nineteen patients also underwent cerebral angiography. The MRI studies were performed with a prototype super-conductive magnet using a 0.6 Tesla or a 1.5 Tesla magnetic field. Two pulse sequence techniques were used resulting in T1 and T2 weighted images. All studies were interpreted descriptively by a single neuroradiologist in a blinded fashion, with special attention to focal parenchymal abnormalities. Patients with previously documented clinical strokes or reversible ischemic neurologic deficits lasting more than 24 hours were excluded. The CT scans revealed focal areas of abnormalities in 7 of 22 patients (32%), while the MRI scans showed focal changes in 17 patients (77%). All the CT lesions were clearly visualized on MRI. The MRI changes were better seen on T2 weighted images as areas of increased signal intensity. There was a marked preponderance of deep hemispheric lesions on both CT and MRI studies. Focal parenchymal abnormalities were not limited to the symptomatic vascular territory. We conclude that MRI reveals focal parenchymal changes in the majority of patients with transient ischemic attacks and is more sensitive than late generation CT scans. However, specificity appears to be poor, and may limit clinical usefulness. While the significance of the MRI "lesions" remains speculative, they may represent markers of chronic cerebrovascular disease in these patients.