Creutzfeldt-Jakob disease in a husband and wife

A 53-year-old man died of sporadic Creutzfeldt-Jakob disease (CJD) after a 1.5-year clinical course. Four and a half years later, his then 55-year-old widow died from CJD after a 1-month illness. Both patients had typical clinical and neuropathologic features of the disease, and pathognomonic proteinase-resistant amyloid protein ("prion" protein, or PrP) was present in both brains. Neither patient had a family history of neurologic disease, and molecular genetic analysis of their PrP genes was normal. No medical, surgical, or dietary antecedent of CJD was identified; therefore, we are left with the unanswerable alternatives of human-to-human transmission or the chance occurrence of sporadic CJD in a husband and wife.     

The "first generation" of endovascular stent-grafts for patients with aneurysms of the descending thoracic aorta

OBJECTIVE: Our goal was to determine whether endovascular stent-grafting is feasible and effective for patients with aneurysms of the descending thoracic aorta. METHODS: Starting in July 1992, we conducted a prospective, uncontrolled clinical trial in 103 patients (mean age 69 years [range 34-89 years]) who underwent endovascular treatment of aneurysms of the descending thoracic aorta using a custom-fabricated, self-expanding stent-graft device. Follow-up was 100% complete and averaged 22 months. Sixty-two patients (60%) were judged not to be reasonable candidates for a conventional "open" surgical procedure. RESULTS: Complete thrombosis of the aneurysm was ultimately achieved in 86 (83%) patients. The early mortality rate was 9% +/- 3% (+/- 70% CL). Multivariable analysis revealed that myocardial infarction or stroke was linked with a higher likelihood of early death (P = .001). Early serious complications included paraplegia in 3% +/- 2% and stroke in 7% +/- 3%. Actuarial survival estimates at 1 year and 2 years were 81% +/- 4% and 73% +/- 5% (+/- 1 SE), respectively; being judged not to be a surgical candidate portended a higher probability of death (P = .003). According to the intent-to-treat principle, "treatment failure" (including all late sudden unexplained deaths) occurred in 38 patients; 53% +/- 10% of patients were free from treatment failure at 3.7 years. Stent-graft related complications occurred commonly and were linked with several anatomic, technical, and patient-related risk factors. CONCLUSIONS: This 5-year clinical trial involving use of a "first generation" device indicates that endovascular stent-grafting of descending thoracic aortic aneurysms is feasible with acceptable medium-term results. More refined, commercially developed devices available today offer less traumatic and more precise stent-graft deployment; these major technical advantages, coupled with important lessons we have learned over time and better patient selection, should be associated with more salutary clinical results in the future.     

Arachidonic acid potentiates the duration of the metabotropic, protein kinase C-mediated, suppression of the inhibitory adenosine A1 receptor pathway in glutamatergic nerve terminals from rat cerebral cortex

Percutaneous US guided nephrostomy is the simplest and most direct technique to drain an obstructed kidney. The indications are included in two groups: temporary drainage and permanent drainage; the former is indicated in the non endoscopically superable ureteral obstruction, in pyonephrosis, in pregnant women and in transplanted kidneys (due to the easier access), the latter is exclusively reserved to neoplastic obstructions. The only real contraindication to the method, besides a documented allergy to local anaesthetics, is represented by a severe coagulopathy. Positioning techniques are the "one shot" technique, in which dilation and positioning are synchronous (it can avoid fluoroscopy but it is more traumatic) and angiographic derived Seldinger's technique, that utilizes fluoroscopy and an instrumentation including a guidewire and a set of Amplatz dilators. Complications are due to the access route; the choice of an intercostal access is always inadvisable, due to the risk of pneumothorax or pulmonary injury; the most frequent complications are vascular (hemorrhage, retroperitoneal hematoma) and usually well controlled; more severe lesions (renal artery laceration and arteriovenous fistula) may require intervention or embolization, but the incidence of nephrectomies due to vascular injury accounts for one per thousand.     

Hepatectomy with hypothermic perfusion of the liver

Whereas most liver resections can be performed within 60 min, the period of vascular clamping and resulting ischemia may prove too short to allow complex major liver resections (MLR) especially on diseased livers. To overcome this problem, cooling of the liver with 4 degrees C preservations solution routinely used in liver transplantation may be used in three different approaches to MLR: I "In situ": the liver remains in the abdomen and integrity of afferent and efferent vessels is conserved. II "Ex situ-in vivo": the liver exteriorized from the abdomen by transecting all hepatic veins, remains connected to the porta hepatis. III "Ex vivo": the liver being removed from the abdomen, the MLR is performed extracorporeally. Of 15 MLR reported here, 11 were performed "in situ" and 4 "ex situ-in vivo"/Nowadays, the liver surgeon's "toolbox" must contain hypothermic liver perfusion. In carefully selected cases, these techniques allow MLR on diseases livers or mandating complex vascular procedures.     

A Hierarchical Approach for Regular Centroidal Voronoi Tessellations

In this paper, we consider Centroidal Voronoi Tessellations (CVTs) and study their regularity. CVTs are geometric structures that enable regular tessellations of geometric objects and are widely used in shape modelling and analysis. While several efficient iterative schemes, with defined local convergence properties, have been proposed to compute CVTs, little attention has been paid to the evaluation of the resulting cell decompositions. In this paper, we propose a regularity criterion that allows us to evaluate and compare CVTs independently of their sizes and of their cell numbers. This criterion allows us to compare CVTs on a common basis. It builds on earlier theoretical work showing that second moments of cells converge to a lower bound when optimizing CVTs. In addition to proposing a regularity criterion, this paper also considers computational strategies to determine regular CVTs. We introduce a hierarchical framework that propagates regularity over decomposition levels and hence provides CVTs with provably better regularities than existing methods. We illustrate these principles with a wide range of experiments on synthetic and real models.     

Proteomic analysis of the response of the human neutrophil-like cell line NB-4 after exposure to anthrax lethal toxin

We used 2‐D DIGE to analyze the early response of NB‐4 cells, a human promyelotic leukemia cell line, exposed to lethal toxin from Bacillus anthracis at the proteome level. After a 2 h exposure, cells were still viable and 43% of spots (n = 1042) showed a significant change in protein level. We identified 59 spots whose expression had changed significantly, and these reflected cytoskeleton damage, mitochondrial lysis and endoplasmic reticulum stress. Actin filament assembly was disrupted as evidenced by an increase in both actin subunits and phosphorylated cofilin, whilst levels of tropomyosin, tropomodulin and actin related protein 2/3 complex subunit decreased. Lower levels of ATP synthase subunits and mitochondrial inner membrane protein were identified as markers of mitochondrial lysis. Levels of various stress response proteins rose and, uniquely, levels of Ca²⁺ binding proteins such as translationally controlled tumor protein rose and hippocalcin‐like protein 1 decreased. This response may have mitigated effects brought about by mitochondrial lysis and endoplasmic reticulum stress, and delayed or prevented apoptosis in NB‐4 cells. These results resemble findings of similar proteomics studies in murine macrophages, although quantitative differences were observed.     

The continuing dilemma concerning medical versus surgical management of patients with acute type B dissections

In the free-running circadian rhythms of 14 human subjects (4 females, 10 males) who lived singly in an isolation unit without temporal clues, locomotor activity was recorded by means of contact plates installed below the carpet in the main room. During sleep, movements in bed were picked up by spring contacts attached to the mattress. In all subjects, the hourly means of locomotion during wakefulness (alpha) were negatively correlated with the duration of alpha to such an extent that the total amount of locomotion per cycle remained constant when alpha varied from 14 to 23 hr. The hourly values of movements in bed were independent of the duration of sleep (rho), so that the total number of movements was almost proportional to rho. The "homeostatic control" of locomotion during wake time is considered as a means to conserve energy when the duration of wakefulness increases.     

Nonmitogenic anti-CD3F(ab')2 fragments inhibit lethal murine graft-versus-host disease induced across the major histocompatibility barrier

We have investigated the in vivo administration of nonmitogenic anti-CD3F(ab')2 fragments for the prevention of lethal graft-vs-host disease (GVHD) in irradiated recipients of fully allogeneic bone marrow cells plus splenocyte (BMS) inocula. Recipients of anti-CD3F(ab')2 fragments administered for 1 mo post-bone marrow transplantation (BMT) had 100% survival without clinical or histopathological evidence of GVHD. Controls given saline injections succumbed by 39 days post-BMT. Similar results were obtained in groups of recipient mice given BMS in which T cells were depleted by in vitro anti-Thy-1.2 plus C' treatment. Further studies were undertaken to define mechanistic differences in the two approaches. Using Ly-5 congenic sources of donor bone marrow and spleen, we determined that anti-CD3F(ab')2 fragments induced TCR modulation and T cell depletion. Mature splenic-derived CD4+ cells were depleted to a greater extent than CD8+ cells. Early post-BMT, recipients receiving injections with control saline had the highest number of CD4+ and CD8+ cells (which may cause GVHD) followed by recipients of anti-CD3F(ab')2 fragments, with the fewest CD8+ cells observed in the anti-Thy-1.2 + C' treated group. CD3+CD4-CD8- cells (which may suppress GVHD generation) were present in higher numbers early post-BMT in recipients given anti-CD3F(ab')2 fragments as compared to recipients given anti-Thy-1.2 + C'-treated BMS. In long term survivors, a mononuclear T cell containing infiltrate without evidence of destruction was observed in sites of GVHD (lung and liver), consistent with a "Quilty" effect, which was not observed in either of the other two groups. Although survivors were tolerant of donor skin grafts and rejected third party grafts, recipients given anti-CD3F(ab')2 fragments but not anti-Thy-1.2 + C'-treated BMS had vigorous anti-host proliferative responses. These results demonstrate that although in vitro anti-Thy-1.2 + C' treatment of BMS (which is highly depletionary) and in vivo administration of anti-CD3F(ab')2 fragments (which is modulatory and less depletionary) are both effective strategies for GVHD, the cellular events involved in achieving GVHD prevention are indeed different.     

Schools as healthful environments: prerequisite to comprehensive school health?

The development of healthy schools to support and nature the well-being of students, teachers, and staff is proposed as a first step toward the goal of comprehensive health education. A focus on healthy schools incorporates elements of an expanded concept of comprehensive health education that demands careful consideration of the physical, psychological, and social environment of the nation's schools--worksite to 51 million (students, teachers, and staff). The active participation of all stakeholders in environmental assessments, health and safety audits, and restructuring of schools is an essential part of the school reform movement. A healthy worksite concept supports the transformation of the school environment to increase "productivity" by enhancing the ability of teachers, staff, and students to function well.