Search

Solitary fibrous tumor (SFT) is a rare mesenchymal tumor that is quite aggressive and prone to recurrence and metastasis. Most SFTs are benign, but the identification of the histological features that define the dedifferentiation of SFTs can predict the aggressiveness of the tumor and the presence of a reserved prognosis. We present a rare case of conventional SFTs with features of malignancy and highlight the diagnostic and therapeutic difficulties related to this case. Computed tomography aspect suggested a possible gastrointestinal stromal tumor. Surgical intervention was performed through median laparotomy and a tumor of approximately 15∕12 cm was found, developed from the level of the right retroperitoneal space, and pushing anteriorly the ascending colon, cecum, and terminal ileum. The immunohistochemical aspect correlated with the histopathological one suggests a SFT most likely malignant. In conclusion, the early diagnosis of SFTs is essential in establishing an appropriate treatment. Immunohistochemistry is indispensable in establishing the diagnosis of SFTs.

Background and Aim: Type 2 diabetes (T2D) and cancer, the most important public health problems nowadays, and the mechanisms between the presence of diabetes and the development of malignancies remain unclear. The leading cause of cancer death in 2020 is attributed to lung cancer. This study aimed to highlight the impact of the association of these two diseases and the predominant histopathological type of lung cancer in the selected group, glycemic imbalance, and information about the course and outlook for these patients., Patients, Materials and Methods: The authors proposed a case-control 10-year period study, between 2007 and 2017, of two groups of patients diagnosed with T2D and lung cancer who underwent hospitalization at the Clinic of Medical Oncology, Emergency County Hospital, Craiova, Romania., Results: Our study showed a higher incidence of lung adenocarcinoma in patients diagnosed with T2D. The inflammatory syndrome is more pronounced in the diabetic group, which is supported by correlations between lactate dehydrogenase (LDH), albumin, and hemoglobin levels., Conclusions: The duration of cancer treatment in lung cancer and the survival rate is strongly influenced by the presence of diabetes as a concomitant disease.

Keratoacanthoma (KA) is an epithelial tumor of the skin, classically considered as having a malignant transformation risk of 15%; however, many authors and the new World Health Organization (WHO) Classification of skin tumors consider KA as an incipient variant of the cutaneous squamous cell carcinoma (SCC). The aims of the study were to assess the clinical, histopathological (HP) and immunohistochemical (IHC) aspects of the KA and the role of these factors in malignancy occurrence. The studied group comprises 194 patients diagnosed with KA or malignant KA, hospitalized in the Clinic of Dermatology, Emergency County Hospital, Craiova, Romania, between 2006 and 2019. There were 83 males and 111 females, aged 34 to 90 years, 57.21% of the patients being from the rural environment. The histopathology diagnosed 51 KAs and 143 malignant KAs (SCCs). Clinical diagnosis had a limited value in detecting the absence or presence of malignancy in the KA lesion, due to a low accuracy (36.08% and 29.89%, respectively) and specificity (23.07% and 27.02%, respectively); therefore, the HP exam of the surgical excision specimen has a paramount importance in establishing the diagnosis. IHC analysis revealed that the immunostainings for apoptosis-associated proteins and keratinocyte proliferative activity [p53, B-cell lymphoma-2 (Bcl-2), Ki-67 and proliferating cell nuclear antigen (PCNA)] provide some arguments to differentiate between KA and SCC in the studied cases. The correlation of clinical, HP and IHC data lead to an accurate diagnosis of KA; moreover, the clinical, HP and IHC data sustain the idea that KA is a particular form of well-differentiated SCC, which require an active therapeutic attitude.

The aim of this study was the characterization of the implantation site through histological and immunohistochemical exams and the evaluation of the changes that appear in the pregnancies ended by spontaneous abortion compared to normal pregnancies ended by requested abortion. One hundred eight patients were divided in two groups: the study group that included 58 patients with spontaneous abortion and the control group that included 50 patients with requested abortion. There has been made uterine curettage in all the cases after a complete preoperative evaluation and the obtained product was sent for histopathological evaluation and immunohistochemical study using a VEGF antibody. Studying the histological sections, we noticed the vasculogenesis stages chronology and then according to the histological aspects of normal pregnancy we noticed the histological changes that occurred at the site of implantation in the cases with pathological pregnancies ended by miscarriage. Our results from this study seem to indicate a correlation between decidual vascular changes and the appearance of miscarriage. In pregnancies ended by miscarriage, we found delays in the trophoblast development according to the gestational age at which the event abortifacient happened. The study emphases the temporal differentiation of utero-placental angiogenesis comparing to villous vasculogenesis and angiogenesis in the first trimester miscarriage and normal pregnancy. At the control group, VEGF expression was positive in 88% of cases, while in the study group, pregnancies ended by spontaneous abortion, positive expression of VEGF was present in only 31% of cases. Our data suggest vascular disorders and are in concordance with other histological and ultrasound studies postulating the idea of a link between miscarriage and placental vascular bed pattern changes.

Event-related potential (ERP) deficits associated with auditory oddball and click-conditioning paradigms are among the most consistent findings in schizophrenia and are discussed as potential biomarkers. However, it is unclear to what extend these ERP deficits distinguish between schizophrenia patients and healthy controls on a single-subject level, which is of high importance for potential translation to clinical routine. Here, we investigated 144 schizophrenia patients and 144 matched controls with an auditory click-conditioning/oddball paradigm. P50 and N1 gating ratios as well as target-locked N1 and P3 components were submitted to conventional general linear models and to explorative machine learning algorithms. Repeated-measures ANOVAs revealed significant between-group differences for the oddball-locked N1 and P3 components but not for any gating measure. Machine learning-assisted analysis achieved 77.7% balanced classification accuracy using a combination of target-locked N1 and P3 amplitudes as classifiers. The superiority of machine learning over repeated-measures analysis for classifying schizophrenia patients was in the range of about 10% as quantified by receiver operating characteristics. For the first time, our study provides large-scale single-subject classification data on auditory click-conditioning and oddball paradigms in schizophrenia. Although our study exemplifies how automated inference may substantially improve classification accuracy, our data also show that the investigated ERP measures show comparably poor discriminatory properties in single subjects, thus illustrating the need to establish either new analytical approaches for these paradigms or other paradigms to investigate the disorder., (© The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Attention deficits, among other cognitive deficits, are frequently observed in schizophrenia. Although valid and reliable neurocognitive tasks have been established to assess attention deficits in schizophrenia, the hierarchical value of those tests as diagnostic discriminants on a single-subject level remains unclear. Thus, much research is devoted to attention deficits that are unlikely to be translated into clinical practice. On the other hand, a clear hierarchy of attention deficits in schizophrenia could considerably aid diagnostic decisions and may prove beneficial for longitudinal monitoring of therapeutic advances. To propose a diagnostic hierarchy of attention deficits in schizophrenia, we investigated several facets of attention in 86 schizophrenia patients and 86 healthy controls using a set of established attention tests. We applied state-of-the-art machine learning algorithms to determine attentive test variables that enable an automated differentiation between schizophrenia patients and healthy controls. After feature preranking, hypothesis building, and hypothesis validation, the polynomial support vector machine classifier achieved a classification accuracy of 90.70% ± 2.9% using psychomotor speed and 3 different attention parameters derived from sustained and divided attention tasks. Our study proposes, to the best of our knowledge, the first hierarchy of attention deficits in schizophrenia by identifying the most discriminative attention parameters among a variety of attention deficits found in schizophrenia patients. Our results offer a starting point for hierarchy building of schizophrenia-associated attention deficits and contribute to translating these concepts into diagnostic and therapeutic practice on a single-subject level., (© The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Skin burns represent a major problem of public health because of their frequency and because of their seriousness, too. The healing process of the burnt wound is extremely complex, as it requires a well-coordinated collaboration among different tissues and cellular strings. From the morphological point of view, the stages of the repairing process of the skin wounds include processes of inflammation, proliferation and tissular remodeling. Angiogenesis has a role of extreme importance within the healing process of third-degree skin burns. That is because the vascularization remake is necessary for feeding the tissue of granulation with nutritive substances and oxygen. The angiogenesis started relatively fast. Three days after the producing of the burn, there could be identified strings of CD34+ endothelial precursor cells at the edges and deep into the wound, all these having contact with the normal blood vessels or with those lees affected by the thermal aggression. After the lumenization of the newly-formed capillary vessels, there appeared the pericytes within their membrane. The CD34+ endothelial precursor cells (EPc), as well as the pericytes, participate at the synthesis of the base membrane of the angiogenesis vessels. The density of the angiogenesis vessels on the surface unit within the tissue of granulation grew from three to 12 days. After that, they reduced progressively while the tissue of granulation was becoming mature. The angiogenesis vessels go through a process of reshuffling and maturation at the same time with the maturation of the tissue of granulation, but these processes did not appear to be finished when the skin was completely healed, and the epidermis was totally recovered.

A prospective study made by authors was initiated in 2000 in order to analyze differences in terms of response rate, overall survival and progression free survival for patients with advanced head and neck carcinoma treated with radiotherapy vs. radiochemotherapy, respectively and to analyze the role of modern molecular biomarkers in the prognosis of these patients (p53, EGFR and Ki67). It was detected one significant difference appeared between the two groups for response rate (p<0.0001) and median overall survival [18.8 months in Group A and 17.2 months in Group B, with a hazard ratio for survival of 0.88 (95% CI, 0.75-1.12, p<0.0001]. Progression free survival was not significant different between these two groups [6.9 months for Group A and 7.2 months for Group B, p=0.3179]. Multivariate analysis by sex, age, TNM stage, site of disease, revealed TNM stage and site of disease as clinical phenotypes with predictive value. Also, the molecular biomarkers p53, EGFR and Ki67 have a prognostic significance in head and neck cancer in addition to the established clinical prognostic factors such as the stage, site of the tumor and the type of treatment. Because of material reasons, we decided to carry out the immunohistochemical marking in the group of patients who were radiochemotherapy-treated and the results of multivariate analysis reached statistical significance threshold in terms of response rate to treatment, overall survival and disease-free interval. Furthermore, immunohistochemical examination was not performed for patients with rhinopharyngeal carcinoma with marked radiochemosensibility and reduced tumor aggressiveness reflected in significantly better therapeutic outcomes by treatment response rate, overall survival and disease free interval. In the present study of the 93 cases that underwent immunohistochemical staining for EGFR, the majority (66 cases) showed a positive reaction for this marker, in 36 cases are highly immunohistochemical staining, and in 30 cases were weakly positive. In addition, cell proliferation was intense in 26 cases in which Ki67 index was greater than 45%, p53 protein expression was positive in 18 cases, but the majority (22) of cases showed a positive reaction for this marker; index was greater than 55%, and in the most (22) cases p53 protein was not expressed. Radio/chemoradiotherapy regimen associated with molecular anti-EGFR target therapy is standard therapy in advanced squamous head and neck carcinoma.

During the healing process of third-degree skin burns, a very complex response involves different cells and tissues linked together by intra- and extra-cellular mechanisms. For the restoration of damaged tissues, angiogenesis is the key point in the formation of new blood vessels. By their emollient, astringent, antiseptic, anti-inflammatory, biostimulator, epithelizing and cicatrizing effect, active principles from natural products contribute to the acceleration of the wound-healing process. In our study, we investigated the angiogenesis process in experimental model of third-degree skin burns treated with three topical preparations (cold-creams) containing 10% herbal extracts, comparing with 1% sulfadiazine cream and cold-cream base respectively. By their biostimulator, epithelizing and cicatrizing effect, cold-creams with herbal extracts are locally modulators of the cellular response and support the wound healing. The phytocomplex stimulates the favorable evolution of the burnt skin wounds and the development of neoangiogenesis capillaries.

Chronic periodontopathies and diabetes mellitus are two clinical entities, which reciprocally condition one another. The periodontal disease is considered a major complication, which induces an unfavorable evolution of diabetes mellitus. Diabetes mellitus is an endocrine disease which favors the occurrence of periodontopathy through gum's microvascular disorders, the selection and development of an aggressive bacterial plaque and through an exaggerate inflammatory response to the microflora within the oral cavity. Both diabetes mellitus and periodontal disease have an increasing incidence in the whole world. Development of periodontopathy is related to the aggression of bacterial flora in dental plaque, flora that is influenced on its turn by the evolution of diabetes mellitus. In our study, we have evaluated the inflammatory reaction in periodontium in patients with slowly and progressive periodontitis in patients with diabetes mellitus who had diabetes longer than five years. It has been found that all patients presented a chronic inflammatory infiltrate, abundant, with round mononuclear cells of lymphocyte, plasma cells and macrophage type, with non-homogenous arrangement, more intensely where the covering epithelium presented erosions or necrotic areas. Out of the immunity system cells, the most numerous where of T-lymphocytes type.

The angiogenesis is a complex process, incompletely understood, regulated by various stimulating and inhibiting angiogenic factors. In the present study, we proposed to evaluate the angiogenic changes that occur in the cases with recurrent pregnancy loss comparing with a control group represented by women with requested abortion. The evaluation of the changes in the vascular bed was made by immunohistochemical methods, evaluating the answer of the curettage products to the mouse anti-human CD31 and CD34 monoclonal antibodies immunolabeling. The endothelial cells reaction to the CD31 antibody was different, very intense in the normal or slightly congestive vessels. The endothelial cells from the strongly congestive vessels had a light and scratchy reaction. We found intense positive reactions in the control group for CD34 in the vessels from the villous axis and also in the vessels from the spongious decidua. In the study group, we found light positive reaction in the vessels from the decidua situated in the proximity of the necrotic areas; we found a light positive reaction also in the vessels and mesenchymal fibroblasts from some chorial villous axis.

Skin burns are a rather high incidence lesions which, depending on their depth and extension, can severely affect not only the skin but the entire organism. Third-degree skin burns extended on over 20% of the body surface often require skin graft. Skin allograft is a therapeutic alternative when autograft cannot be used. We investigated the allograft influence on the angiogenesis process in third-degree skin burns, using an experimental model. We noticed that the allograft induces a stronger inflammatory reaction associated with intense angiogenesis process by about 10-15% compared to control group.

Local cellular response plays a major role in restoring skin integrity, in burns with infectious complications, chronic fibrous sequelae, etc. For the study of wound-healing process, different experimental models of skin burn were developed. Mice, rats, rabbits and guinea pigs are the most used laboratory animals, kept under standard conditions of light, temperature, food and water (ad libitum). Commonly, by intramuscular injection, general anesthesia was induced with ketamine hydrochloride. Most times, skin burns were inflicted on the dorsal region of animals. Metal devices with different shapes and weights, heated in water at various temperatures were applied locally, for few seconds. The paper reports on 65 natural medicinal products recommended for the external and internal treatment of skin damages (first- or second-degree burns, various wounds, ulcerations). Some of them are traditionally used in the Romanian ethnopharmacology, supporting the wound-healing process mainly because of their epithelizing, astringent, emollient, demulcent, anti-inflammatory, antimicrobial, immunomodulatory and antioxidant properties.

Macrophages are some of the innate immune cells with a central role in inflammatory and immune responses. Studies in the last 20 years have shown that these cells have a particular influence in the reparative processes also. Our aim in this study was to evaluate the macrophage response in third-degree skin burns treated with allograft in an experimental model. Macrophages were specifically highlighted by immunohistochemical staining with anti-CD68 antibody. In the first evolutive part of the reparatory process, macrophages rapidly increased both numerically and as a relative area with about 300%, and then decreased progressively along with the granulation tissue maturation. Macrophage overall response curve was similar in animals treated with allograft and in the control group (untreated), which leads us to believe that the allograft does not induce a more ample immune response that could be regarded as pathological.

In the past 30 years, after the discovery of vascular proliferation factors, angiogenesis is one of the most intensively studied fields. Restoring the vascular network after burn injury is essential for healing, as it brings oxygen and nutrients to injured tissues, improves the contribution of inflammatory cells and prepares the damaged area for repair and tissue regeneration. To study the process of angiogenesis we used seven groups of five animals, each of adult Wistar rats, which were inflicted with third degree skin burns. From each group of animals, we sampled at successive intervals of three days the entire burnt wound with a ring of surrounding normal skin. Sampled skin fragments were processed for paraffin inclusion, sectioned with a microtome and stained with Hematoxylin-Eosin or Masson trichrome. The samples were also analyzed using single chromogenic immunohistochemistry or double immunofluorescence for the presence of CD34 and alpha smooth muscle actin (α-SMA). Angiogenesis process started at about three days after the burn infliction, with the appearance of tubular structures lined by CD34-positive cells. Subsequently, these cells showed intense proliferative activity that generated a network that included progressive neovascularization around the wound surface. Maximum vascular proliferation occurred at 9-15 days after injury, when the number of capillaries reached 229/mm², and the total area of capillary angiogenesis at 100.27 μm² (about 10% of the section area). Subsequently, the process of angiogenesis was gradually reduced, but remained at moderate levels after wound healing. During the process of angiogenesis, there was a very close relationship between CD34-positive cells and pericytes (as α-SMA-positive).

Laryngocele is an abnormal dilatation of Morgagni ventricle (saccule) in direct communication with the laryngeal lumen. Symptoms are not characteristic: hoarseness, dyspnea, foreign body sensation and cough. Sometimes it is presented as cervical swelling causing airway obstruction and need an emergency tracheotomy. In this paper, we report a case of upper airway obstruction due to laryngocele associated with a laryngeal carcinoma who was treated by emergency tracheotomy and, finally by total laryngectomy. A review of the literature is also presented.

At European level, Romania unfortunately comes first as far as mortality due to cervical cancer is concerned, mortality rate recording a continuous increase due to disease detection in advanced stages. In this context, we followed an assessment of women's cognitive and attitudinal fund in relation to early detection of cervical cancer, through the application of a questionnaire on a batch of 617 women with ages from 18 to 75-year-old, with various levels of education, residents of Craiova City and communes from Dolj County. Statistic processing of their answers indicates that 43.3% of the inquired subjects have not had a routine gynecological exam for at least seven years (or even never), which is more often found in the subgroup of women from the rural environment, with ages over 35 years and with an elementary educational level (p<0.001). 65.8% of the women have not done a Babes-Papanicolau test for seven years or even never, residence area, age and education level being once again discrimination factors between the subgroups. The reasons usually put forward as a justification for the failure to do the cytological test for the past three years are negligence (23.8%), the lack of information on the existence of such an investigation (18.2%), the absence of a genital pathology (12.8%) or of a medical recommendation (11.8%). Results suggest the need to provide uniform accessibility of the population to health services, by developing and implementing new strategies of educational and sanitary intervention mainly in rural communities.

The study focuses on the possible influences of intra (I) lobular (L) stromal compounds [intertubular spaces and seminiferous (S) tubule (T) wall (W)] morphologic changes on S epithelium (E) during ageing process. The material consisted of surgical samples of testicular tissue from 192 patients with orchidectomy for prostate carcinoma. Seven age groups were designed, from 50 to 80 years. Tissue samples were fixed in neutral buffered formalin, embedded in paraffin stained with HE, Goldner and Gömöri and immunomarked (in a subgroup of 28 cases) for smooth muscle actin, collagen IV, and CD34. SE had an uneven involution, both individually and inter-individually, but with normal spermatogenesis in many of ST. E degenerative changes were seen mainly in L periphery. Different stages of maturation arresting were more frequent in older patients. IL septae had changes with extremely variable intensity, dispersed mainly in L periphery, without significant spread and without extensive trend with ageing. Leydig cells showed focal hyperplasia without extensive trend related with ageing. STW presented strictly in the internal layer of lamina propria (apposed to basement membrane of ES) a focal sclerosis, with variable extension concerning its presence, thickness and T circumference (T without sclerosis, with focal sclerosis and with fibro-hyaline "collar" - FHyC) but not related with ageing. IL arteriolae showed focal areas of degeneration with a wide individual and inter-individual range of intensity and extension, but not related with age. Capillary network (CN), with both its peri-T and intramural segments, was present in all age groups, with no quantitative endothelial changes and decreasing only in very old cases. FHyC was often associated with E atrophy. STW focal sclerosis could explain focal degeneration of SE in senescence, although CN undergoes no significant changes.

Background: Elastography is an imaging technique, which displays the hardness of soft tissue, by showing the behavior of tissue when subjected to mechanical stress. The purpose of this study was to assess the role of ultrasound elastography in differential diagnosis of breast lesions., Materials and Methods: A prospective study was conducted in our Research Centre, University of Medicine and Pharmacy of Craiova. We introduced in this prospective study 215 patients diagnosed with breast lesions between January 2009 and January 2011. The patients were examined in the supine position and a ductal exploration was made over the breast. The final diagnose was cytology (FNA - fine needle aspiration), histology after excision or follow-up for six months. For obtaining the elastography images, we used a EUS Hitachi EUB 8500 and Siemens ultrasound systems with elastography modules incorporated. For assessment of ultrasound elastography role in differential diagnosis of breast lesions, we performed ROC analysis., Results: The elasticity score for benign lesions was on average 1.95±1.1, and for malignant lesions was 4.21±0.9. The mean diameter of malignant lesions was 27.3 mm, which was higher than the average diameter of benign lesions (19.9 mm). The most common histology of the benign nodules was fibroadenomas, cysts, and fibrocystic change. Of the malignant nodules, the most common lesion was infiltrative ductal carcinoma. We obtained a sensitivity of 85.3%, and a specificity of 90% (area under the ROC curve=0.908, 95%CI=0.856-0.945 and p=0.0001) when a cut-off point of 3 was used., Conclusions: Elastography is a method which can complement conventional ultrasound by improving the diagnostic performance. The introduction of ductal ultrasound combined with elastography increased the sensitivity and specificity, the radial technique allowing the precise localization of lesions regarding the breast gland.

Introduction: Malignant melanoma rarely develops in the mucous membranes. Statistical data indicate that rhinosinusal mucosal melanoma was reported in less than 1% of all melanic tumors and in 2-8% of all cancers developed in the nasal fossae and sinuses. Due to reduce and non-specific symptoms and a high degree of invasion away, patients come for a medical expertise in advanced stages of the disease, which is leading to a poor prognosis. The average five-year survival is 20-30%., Patient and Methods: We present the case of a 65-year-old female patient coming from a rural environment, hospitalized for unilateral nasal obstruction and nasal mucosal changes of a blackish appearance on all of the walls., Results: The endoscopic examination revealed a matter and of a blackish appearance nasal mucosa along the whole length of the left nasal cavity (septum, turbinates, floor, ceiling). Presumptive diagnosis of melanoma led to the excision of inferior and middle turbinate mucosa, floor and ceiling mucosa and the excision of the nasal septum, keeping the columella and the posterior portion. Histopathological and mostly immunohistochemical exams confirmed the diagnosis of malignant melanoma. To determine the phenotype of tumor cells, it was evaluated their immunostaining for HMB-45, Melan-A, S-100, vimentin, cyclin D1 and CD44 markers. The patient followed oncologic treatment and radiochemotherapy, presenting a favorable evolution with the absence of loco-regional recurrence or distant metastasis 24 months postoperatively.

Pericytes and myofibroblasts are two types of connective cells that appear in large quantities in reparative processes. In order to evaluate their response and any relationships between them, we have inflicted third degree skin burns to seven groups of five common Wistar rats each from which we sampled granulation tissue at three days interval for histological and immunohistochemical studies. Alpha-SMA and CD34 antibodies revealed that granulation tissue myofibroblasts do not express CD34 and do not arise from pericytes. The parallel arrangement of myofibroblasts in relation to the burned wound surface suggests that their main function is mechanical traction on granulation tissue and wound edges.

A single force pulse was applied unexpectedly to the arms of five normal human subjects during nonvisually guided planar reaching movements of 10-cm amplitude. The pulse was applied by a powered manipulandum in a direction perpendicular to the motion of the hand, which gripped the manipulandum via a handle at the beginning, at the middle, or toward the end the movement. It was small and brief (10 N, 10 ms), so that it was barely perceptible. We found that the end points of the perturbed motions were systematically different from those of the unperturbed movements. This difference, dubbed "terminal error," averaged 14.4 +/- 9.8% (mean +/- SD) of the movement distance. The terminal error was not necessarily in the direction of the perturbation, although it was affected by it, and it did not decrease significantly with practice. For example, while perturbations involving elbow extension resulted in a statistically significant shift in mean end-point and target-acquisition frequency, the flexion perturbations were not clearly affected. We argue that this error distribution is inconsistent with the "equilibrium point hypothesis" (EPH), which predicts minimal terminal error is determined primarily by the variance in the command signal itself, a property referred to as "equifinality." This property reputedly derives from the "spring-like" properties of muscle and is enhanced by reflexes. To ensure that terminal errors were not due to mid-course voluntary corrections, we only accepted trials in which the final position was already established before such a voluntary response to the perturbation could have begun, that is, in a time interval shorter than the minimum reaction time (RT) for that subject. This RT was estimated for each subject in supplementary experiments in which the subject was instructed to move to a new target if perturbed and to the old target if no perturbation was detected. These RT movements were found to either stop or slow greatly at the original target, then re-accelerate to the new one. The average latency of this second motion was used to estimate the voluntary RT for each subject (316 ms mean). Additionally, we found that the hand neither exerted target-oriented force against the handle nor drifted toward the desired end point just before coming to rest, making it unlikely that the mechanical properties of the manipulandum prevented the hand from reaching its intended target.