DF Patients Research Articles

Sub-acute delayed failure of subthalamic DBS in Parkinson's disease: The role of micro-lesion effect

Objective To study delayed failure after subthalamic nucleus (STN) deep brain stimulation in Parkinson's disease (PD) patients. Methods Out of 56 consecutive bilaterally STN-implanted PD patients, we selected subjects who, after initial clinical improvement (⩾1 month after surgery), lost benefit (delayed failure, DF). Results Five patients developed sub-acutely severe gait disorders (DF). In 4/5 DF patients, a micro-lesion effect, defined as improvement without stimulation, was observed; immediate post-operative MRI demonstrated electrode located above or behind to the STN. Conclusions Patients presenting micro-lesion effect should be carefully monitored, as this phenomenon can mask electrodes misplacement and evolution in DF.

Is diabetic dermopathy a sign for severe neuropathy in patients with diabetes mellitus? Nerve conduction studies and symptom analysis

Objective To assess if diabetic dermopathy (DD) is a sign for severe polyneuropathy (PNP). Methods We investigated the clinical and electrophysiological characteristics of 166 diabetic men (59.5+11.1 years) with different degrees of peripheral nerve involvement. Results All of the clinical variables were more common in patients with diabetic foot ulcers (DF) than in patients with sole PNP ( P<0.001). Only the loss of superficial and vibration sense was more common in the DF patients than the DD patients ( P<0.02). Nerve conduction studies showed the mean compound muscle action potentials (CMAP) were smaller in the DD and DF patients than the PNP patients for peroneal, median and ulnar nerves ( P<0.01). The mean nerve conduction velocities (NCV) of all nerves were slower in the DD and DF patients in compared to sole PNP patients ( P<0.01). The mean distal latencies (DL) of the DD/DF patients were longer than the PNP group. Conclusions The DD and DF patients did not significantly differ in CMAP, NCV, and DL. Significance: Both clinical and electrophysiological features of DD and DF are similar, and significant different than PNP alone. These results suggest that DD is an important clinical sign for more severe neuropathic impairment.

Time-Related Changes in the Incidence, Severity, and Clinical Outcome of Hepatic Veno-Occlusive Disease in Hematopoietic Stem Cell Transplantation Patients During the Past 10 Years

Veno-occlusive disease (VOD) of the liver occurs in 10% to 50% of patients after hematopoietic stem cell transplantation (HSCT), ranging from a mild reversible disease to a fulminant course with a mortality rate close to 100%. We retrospectively evaluated the clinical signs, diagnosis, prognosis, therapy, and outcome of 13 hepatic VOD cases which developed after HSCT. A total of 193 consecutive patients (age: 15–62 years; median 33 years) with various hematologic diseases underwent 197 HSCT (allogeneic HSCT, n = 128; autologous HSCT, n = 69). In general, the conditioning regimen consisted of cyclophosphamide combined either with total body irradiation or busulfan. Since 2000, to reduce hepatic complications, all patients received ursodexycolic acid and discontinuation of norethisterone which inhibits ovulation. VOD diagnosed clinically was mainly managed in supportive fashion. Five patients received thrombolytic therapy (t-plasminogen activator [t-PA], n = 3; defibrotide [DF], n = 2). VOD developed in 13 of 197 cases (6.6%). All except one were in the allogeneic group who had received a busulfan-containing conditioning regimen; Ten (77%) were severe. Thirty-three of 197 (17%) cases died before day 100 with VOD as the cause in eight (24%). All of the t-PA administered patients died with significant hemorrhagic complications. DF patients improved completely, even after renal and respiratory failure, despite high total bilirubin levels. Only one patient who received DF became a long-term survivor; the other died with sepsis during the following days. The dramatic improvement with regard to VOD during DF therapy was encouraging.

Tissue plasminogen activator induced by dengue virus infection of human endothelial cells.

Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) are severe complications of dengue virus (DV) infection. However, the pathogenesis of hemorrhage induced by dengue virus infection is poorly understood. Since endothelial cells play a pivotal role in the regulation of hemostasis, we studied the effect of DV infection on the production of tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) in vitro using both primary isolated endothelial cells, human umbilical cord veins cells, and a human microvascular endothelial cell line. DV infection significantly induced the secretion of tPA but not PAI-1 of human endothelial cells. In addition, tPA mRNA of endothelial cells was induced by DV as demonstrated by RT-PCR. Antibody against IL-6 but not control antibody inhibited DV-induced tPA production of endothelial cells. Furthermore, a good correlation between sera levels of IL-6 and tPA was found in DHF but not DF patients. These results suggest that IL-6 can regulate DV-induced tPA production of endothelial cells, which may play important roles in the pathogenic development of DHF/DSS.

High Levels of Plasma Dengue Viral Load during Defervescence in Patients with Dengue Hemorrhagic Fever: Implications for Pathogenesis

Studies of the pathogenesis of dengue hemorrhagic fever (DHF), a potentially life-threatening disease, have revealed the importance of initial high levels of virus replication. However, the possible involvement of virus during the transition from fever to defervescence, a critical stage in determining the severity of disease, has not been appreciated. Using quantitative reverse transcription-polymerase chain reaction, we examined the levels of plasma dengue viral load during both fever and defervescence periods in patients from a DEN-3 outbreak in southern Taiwan in 1998. Higher levels of plasma dengue viral RNA were found in DHF patients than in DF patients. During defervescence, while the level of plasma dengue viral RNA was undetectable in most DF patients, it remains high in all DHF patients. Using a modified immunoprecipitation assay, we demonstrated for the first time that the plasma dengue viruses persisting during defervescence were in the immune complexes for most DHF patients. These findings suggest that continued active viral replication or delay in the clearance of viremia contributes to the pathogenesis of DHF. Moreover, high levels of plasma dengue viral RNA during defervescence may serve as a disease marker for DHF.

Minor segmental dyssynergy reflects extensive myocardial damage and global left ventricle dysfunction in chronic Chagas disease

The majority of patients with Chagas disease (ChD) remain for 10 to 30 years or even for life in the indeterminate form (IF) of this disease. They have positive-specific serology tests for ChD, but no symptoms or physical signs, and normal findings for electrocardiograms (ECGs) and heart, esophagus, and colon radiographs. To investigate whether patients in this phase of disease have any impairment of left ventricular (LV) systolic performance, we assessed their contractility index by the slope of the LV end-systolic pressure-dimension (Pes-Des) relation. We studied 35 patients with ChD (14 IF, 11 digestive form [DF], 10 cardiac form [CF]) and 13 healthy subjects. Patients with the CF had only minor cardiac involvement (bundle-branch block, normal LV ejection fraction). All patients had normal baseline global LV systolic function on 2-dimensional echocardiography, but minor segmental wall motion abnormalities were observed in 3 DF, 3 IF, and 2 CF patients. At rest and during intravenous phenylephrine infusion, we measured LV dimensions by echocardiography, and LV end-systolic pressure was estimated by a calibrated carotid pulse tracing. We also measured percent fractional shortening (%ΔD) and the rate-corrected mean velocity of fiber shortening (Vcfc). Mean values (± SD) of %ΔD and Vcfc were not significantly different from those exhibited by healthy control subjects in any of the ChD groups at rest (except for CF) or at peak stress using phenylephrine. The Pes-Des slope was similarly and significantly reduced in all ChD patients (IF: 50.7 ± 25; DF: 52.3 ± 24; CF: 60.8 ± 22 mm Hg/cm) compared with normal subjects (89 ± 17 mm Hg/cm). The Pes-Des slope was even more depressed (39.6 ± 10 mm Hg/cm) in ChD patients who had minor segmental wall motion abnormalities (SWMAs) on the baseline 2-dimensional echocardiograph in comparison with the slightly reduced values found in patients with CF who had isolated conduction abnormalities on the ECG (71.8 ± 10 mm Hg/cm). Although %ΔD and Vcfc, even at peak afterload, do not differentiate ChD patients from normal controls, the Pes-Des slope is significantly impaired in IF, DF, and CF patients. The remarkably lower Pes-Des slope value documented in ChD patients exhibiting only minor LVWMAs suggests a more extensive myocardial damage in this group of patients, indicating that they should be considered as exhibiting symptoms of the CF version of the disease. (J Am Soc Echocardiogr 2002;15:610-16.)

INTERNATIONAL TRIAL OF LONG-TERM DEXFENFLURAMINE IN OBESITY

In a randomised, placebo-controlled, double-blind study, 822 obese patients of both sexes were given either dexfenfluramine (dF), 15 mg twice daily (404), or placebo (418) in addition to a calorie-restricted diet for 1 year. Patients in both groups lost weight significantly in the first 6 months; after 6 months dF patients had a higher cumulative mean weight loss. Dropout rates were lower in dF patients than in placebo patients, mainly because of dissatisfaction with weight loss in the latter group. More than twice as many dF patients as placebo patients achieved a given weight loss; but more dF patients than placebo patients had transient side-effects (tiredness, diarrhoea, dry mouth, polyuria, and drowsiness).