Human V5/MT+: comparison of functional and cytoarchitectonic data

To date, the delineation of the human visual “motion area” still relies on functional paradigms originally devised to identify monkey area MT. Using fMRI, we have identified putative human area V5/MT+ in normals by modelling the BOLD responses to alternating radially moving and stationary dot patterns. Functional activations were compared with cytoarchitectonic probability maps of its putative correlate area hOc5, which was calculated based upon data from histological sections of ten human post-mortem brains. Bilateral visual cortex activations were seen in the single subject dynamic versus stationary contrasts and in the group random-effects analysis. Comparison of group data with area hOc5 revealed that 19.0%/39.5% of the right/left functional activation was assigned to the right/left hOc5. Conversely, 83.2%/53.5% of the right/left hOc5 was functionally activated. Comparison of functional probability maps (fPM) with area hOc5 showed that 28.6%/18.1% of the fPM was assigned to hOc5. In turn, 84.9%/41.5% of the area hOc5 was covered by the respective fPM. Thus, random-effects data and fPMs yielded similar results. The present study shows for the first time the correspondence between the functionally defined human V5/MT+ and the post-mortem cytoarchitectonic area hOc5.     

Intraabdominal infections and gut origin sepsis

Intraabdominal postoperative or posttraumatic infections remain a major threat to life in spite of generation after generation of increasingly effective antimicrobial drugs indicating the importance of immunological host defense failure following major trauma or surgical complications. The spectrum of infectious postoperative or posttraumatic complications can, in part, be explained by pathogenic factors inherent to the methodology of modern surgical intensive care and techniques. This report presents a survey of the historical background as well as current concepts of the multiple systems organ failure syndrome as related to postoperative or posttraumatic intraabdominal infectious complications. The pathophysiology of nosocomial infectious complications in the intensive care unit setting is analyzed. The concept of gut origin sepsis is presented and possible preventive and therapeutic actions discussed. A judicious use of antimicrobial drugs on strict indications is emphasized as is the importance of increased knowledge of the interactions between the gut flora, antibiotics, and absence of enteral nutrition.

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Resumen Las infecciones intraabdominales postoperatorias o postraumáticas siguen representando una amenaza grave para la vida a pesar de generación tras generación de drogas antimicrobianas de creciente efectividad, lo cual señala la importancia de la falla de los mecanismos inmunes de defensa del huésped que se presenta después de trauma mayor o acompanando las complicaciones quirúrgicas. El espectro de las complicaciones infecciosas postoperatorias o postraumáticas puede ser explicado en parte por factores patogénicos inhérentes a la tecnología y metodología del moderno cuidado intensivo del paciente en estado crítico. El presente informe reporta una revisión de los antecedentes históricos y de los conceptos actuales sobre el sindrome de falla orgánica multisistémica relacionado con complicaciones infecciosas intraabdominales postoperatorias o postraumáticas. Se analiza la patofisiología de las complicaciones infecciosas nosocomiales en el marco de la unidad de cuidado intensivo. Se hace énfasis sobre el uso juicioso de drogas antimicrobianas según indicaciones estrictas, asi como sobre la importancia de un mayor conocimiento sobre las interacciones entre la flora intestinal, los antibióticos, y la ausencia de nutrición enterai.

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Résumé Les infections intra-abdominales postopératoires ou post-traumatiques continuent de menacer le pronostic vital malgré une amélioration constante des antibiotiques ce qui met l'accent sur l'échec des moyens de défense immunologiques après les traumatismes majeurs ou les complications chirurgicales. Le spectre des complications infectieuses postopératoires ou post-traumatiques peut, en partie, être expliqué par des facteurs pathogéniques inhérents à la méthode des soins intensifs et techniques modernes. Ce travail présente l'historique et les concepts actuels de défaillance polyviscérale en rapport avec des complications infectieuses intra-abdominales postopératoires ou post-traumatiques. La pathophysiologie des complications infectieuses nosocomiales dans l'unité des soins intensifs est analysée. La conception de sepsis d'origine intestinale est présentée et les actions préventive et thérapeutique sont discutées. L'utilisation judicieuse des antibiotiques est soulignée, ainsi que les interactions entre la flore intestinale, les antibiotiques et l'absence de nutrition entérale.

     

The “jerky dystonic unsteady hand”: A delayed motor syndrome in posterior thalamic infarctions

We report the cases of three patients with a thalamic infarct in the territory of the posterior choroidal artery involving the posterior thalamic nuclei. These patients developed delayed complex hyperkinetic motor syndromes, associating ataxia, tremor, dystonia, myoclonus and chorea, which we call the jerky dystonic unsteady hand. One patient had a severe myoclonic and ataxicdystonic choreoathetosis; another showed a so-called rubral tremor (myoclonic ataxia with resting, action, and wing-beating tremor) with dystonia; and the third one had a dystonic and ataxic hand with intermittent mild action myoclonus. All of them had sensory dysfunction; two had also presented with a painful Dejérine-Roussy syndrome. All had CT or MRI-proven infarcts in the territory of the posterior cerebral artery involving the posterior choroidal territory with an abnormal signal in the posterior area of the thalamus (pulvinar nucleus) but sparing the other thalamic, subthalamic and midbrain structures. These delayed myoclonic complex hyperkinetic syndromes have not been reported before, and we did not observe them in other topographic forms of thalamic infarcts. They may thus represent a new entity of movement disorders due to lesions in the posterior thalamic nuclei, with specificity for posterior choroidal artery infarcts.     

Antitumor vaccination of patients with glioblastoma multiforme: a pilot study to assess feasibility, safety, and clinical benefit.

PURPOSE: Prognosis of patients with glioblastoma is poor. Therefore, in glioblastoma patients, we analyzed whether antitumor vaccination with a virus-modified autologous tumor cell vaccine is feasible and safe. Also, we determined the influence on progression-free survival and overall survival and on vaccination-induced antitumor reactivity. PATIENTS AND METHODS: In a nonrandomized study, 23 patients were vaccinated and compared with nonvaccinated controls (n = 87). Vaccine was prepared from patient's tumor cell cultures by infection of the cells with Newcastle Disease Virus, followed by gamma-irradiation, and applied up to eight times. Antitumor immune reactivity was determined in skin, blood, and relapsed tumor by delayed-type hypersensitivity skin reaction, ELISPOT assay, and immunohistochemistry, respectively. RESULTS: Establishment of tumor cell cultures was successful in approximately 90% of patients. After vaccination, we observed no severe side effects. The median progression-free survival of vaccinated patients was 40 weeks (v 26 weeks in controls; log-rank test, P = .024), and the median overall survival of vaccinated patients was 100 weeks (v 49 weeks in controls; log-rank test, P < .001). Forty-five percent of the controls survived 1 year, 11% survived 2 years, and there were no long-term survivors (> or = 3 years). Ninety-one percent of vaccinated patients survived 1 year, 39% survived 2 years, and 4% were long-term survivors. In the vaccinated group, immune monitoring revealed significant increases of delayed-type hypersensitivity reactivity, numbers of tumor-reactive memory T cells, and numbers of CD8(+) tumor-infiltrating T-lymphocytes in secondary tumors. CONCLUSION: Postoperative vaccination with virus-modified autologous tumor cells seems to be feasible and safe and to improve the prognosis of patients with glioblastomas. This could be substantiated by the observed antitumor immune response.     

Longitudinal neurological follow-up of a group of HIV-seropositive and HIV-seronegative hemophiliacs: results from the hemophilia growth and development study

BACKGROUND: Boys and young men with hemophilia treated with factor infusions before 1985 had a substantial risk of acquiring the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome. This study was designed to assess the effects of HIV and hemophilia per se on neurological function in a large cohort of subjects with hemophilia, and to investigate the relationships between neurological disease and death during follow-up. METHODS: Three hundred thirty-three boys and young men (207 HIV seropositive and 126 HIV seronegative) were evaluated longitudinally in a multicenter, multidisciplinary study. Neurological history and examination were conducted at baseline and annually for 4 years. The relationship between neurological variables, HIV serostatus, CD4+ cell counts, and vital status at the conclusion of the study was examined using logistic regression models. RESULTS: The risks of nonhemophilia-associated muscle atrophy, behavior change, and gait disturbance increased with time in immune compromised HIV-seropositive subjects compared with HIV seronegative or immunologically stable HIV-seropositive subjects. The risk of behavior change in immune compromised HIV-seropositive hemophiliacs, for example, rose to 60% by year 4 versus 10% to 17% for the other study groups. Forty-five subjects (13.5%), all of whom were HIV seropositive, died by year 4. Subjects who died had had increased risks of hyperreflexia, nonhemophilia-associated muscle atrophy, and behavior change. CONCLUSIONS: These results indicate that immune compromised, HIV-seropositive hemophiliacs have high rates of neurological abnormalities over time and that neurological abnormalities were common among subjects who later died. By contrast, immunologically stable HIV-seropositive subjects did not differ from the HIV-seronegative participants. Hemophilia per se was associated with progressive abnormalities of gait, coordination, and motor function.     

Immediate Obturation of the Surgical Defect after Partial Maxillectomy in the Endentulous Patient

Closure of the surgical defect immediately after partial maxillectomy is the treatment of choice. The advantages are: maintaining facial contour, rapid re-establishment of speech, swallowing and mastication. A number of methods for the fixation of the immediate obturator in patients without teeth have been described. A new technique is reported where a transnasal wire holds the existing denture in position after partial maxillectomy. The method has been carried out on 7 patients with sino-nasal cancer during the period 1978-1994. The advantages of the technique are that the wire acts as an axis of rotation which together with the sponge in the cavity provide good stability of the denture. There is minimal preoperative laboratory work and simplification in replacing the surgical dressing.     

Phase I study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, combined with cytarabine in patients with refractory leukemia.

PURPOSE: Cloretazine (VNP40101M) is a novel sulfonylhydrazine alkylating agent with significant antileukemia activity. A phase I study of cloretazine combined with cytarabine (1-beta-d-arabinofuranosylcytosine, ara-C) was conducted in patients with refractory disease. DESIGN: Ara-C was given i.v. at a fixed dose of 1.5 gm/m(2)/d by continuous infusion for 4 days (patients ages <65 years at time of diagnosis) or 3 days (patients ages > or =65 years). Cloretazine was given i.v. over 15 to 60 minutes on day 2 at a starting dose of 200 mg/m(2), with escalation in 100 mg/m(2) increments in cohorts of three to six patients until a maximum tolerated dose was established. The DNA repair enzyme O(6)-alkylguanine DNA alkyltransferase (AGT) was measured at baseline. RESULTS: Forty patients, including 32 with acute myeloid leukemia, received 47 courses of treatment. Complete responses were seen at cloretazine dose levels of > or =400 mg/m(2) in 10 of 37 (27%) evaluable patients, and in this patient subset, AGT activity was significantly lower in patients that responded to treatment than in patients who did not (P < or = 0.027). Dose-limiting toxicities (gastrointestinal and myelosuppression) were seen with 500 and 600 mg/m(2) of cloretazine combined with the 4-day ara-C schedule but not seen with the 3-day schedule. CONCLUSION: The recommended cloretazine dose schedule for future studies is 600 mg/m(2) combined with 1.5 gm/m(2)/d continuous infusion of ara-C for 3 days. The cloretazine and ara-C regimen has significant antileukemic activity. AGT activity may be a predictor of response to cloretazine.     

Disseminated Bartonella henselae disease mimicking Langerhans’ cell histiocytosis

Bartonella henselae, the causative agent of cat‐scratch disease, has been recognized to be responsible for a broad range of clinical syndromes. We report the case of a patient with disseminated B. henselae infection mimicking Langerhans cell histiocytosis at presentation and its successful management with neurosurgery, prolonged antibacterial therapy, and observation.     

Concomitant MDS with isolated 5q deletion and MGUS: case report and review of molecular aspects

Patients with monoclonal gammopathy of undetermined significance (MGUS) have a higher risk for the development of concomitant primary cancers such as multiple myeloma (MM) and myelodysplastic syndrome (MDS). We report the case of patient initially suffering from MGUS of the IgG lambda subtype for more than 10 yr, which evolved to MM and MDS with deletion (5q) with severe pancytopenia. Due to pancytopenia, he received dose‐reduced treatment with lenalidomide and dexamethasone. He achieved an ongoing transfusion independency after about 1 month of treatment. Bone marrow taken 14 months after start of treatment showed a complete cytogenetic response of the del(5q) clone and a plasma cell infiltration below 5%. In contrast to the development of MM in MGUS patients, the subsequent occurrence of MDS after diagnosis of MGUS is infrequent. Moreover, the biological association of MDS with MGUS is not sufficiently understood, but the non‐treatment‐related occurrence supports the pathogenetic role of pre‐existing alterations of stem cells. Here, we summarize data on concomitant MDS and MGUS/MM with particular emphasis on molecular aspects.