Dorsal column input to inferior raphe centralis neurons

In anesthetized decerebellate cats with additional decerebration or decortication and with one of two types of cervical spinal lesions which either eliminated the dorsal half of the spinal cord or spared the dorsal funiculi, peripheral electric and localized natural stimuli activated neurons in the inferior raphe nuclear complex. Medial lemniscal as well as direct dorsal funicular stimulation was also effective. The majority of raphe neurons activated by stimulation of the dorsal funiculi were also discharged by ventrolateral funicular stimulation.     

Anomalous Inferior Vena Cava Drainage to the Left Atrium With Successful Staged Repair in a 32-Year-Old Woman With Arthritis

This report describes a case involving anomalous drainage of inferior vena cava (IVC) to the left atrium diagnosed when the patient was 32 years old. The tricuspid valve and the right ventricle were small. Successful surgical repair was performed, with significant improvement of the patient’s clinical status. The use of exercise testing with pulse oxymetry monitoring aided in the decision of timing for closure of the iatrogenically created atrial septal defect.     

Prospective analysis of creatine kinase muscle-brain fraction and comparison with troponin T to predict cardiac risk and benefit of an invasive strategy in patients with non-ST-elevation acute coronary syndromes

OBJECTIVE: We sought to determine whether elevation of plasma creatine kinase muscle-brain fraction (CK-MB) would be useful to triage patients with acute coronary syndromes (ACS) to early angiography/revascularization. BACKGROUND: It is unknown whether the measurement of CK-MB is effective for triage to an aggressive management strategy. METHOD: Patients in the Treat Angina With Aggrastat and Determine Cost of Therapy With an Invasive or Conservative Strategy (TACTICS-TIMI) 18 study received aspirin, heparin, and tirofiban for treatment of ACS, were randomized to an invasive or a conservative strategy (angiography/revascularization between 4 and 48 h), and were followed up for a composite end point of death, myocardial infarction, or rehospitalization for ACS.Of 2,220 patients, CK-MB was elevated in 826 (37%). Of the patients with negative CK-MB, troponin T was elevated in 361 (31.2%). Event rates at 30 and 180 days were twice as high in patients with elevated CK-MB than in patients without elevated CK-MB. Both groups had similar benefit from an invasive strategy; there was no evidence of interaction between CK-MB elevation and strategy on the composite end point at 30 or 180 days. When patients were stratified according to both CK-MB and troponin status, there was evidence of a benefit in the invasive strategy among patients who were CK-negative but troponin-positive (odds ratios [95% confidence interval]: 0.13 [0.04 to 0.39] at 30 days and 0.29 [0.16 to 0.52] at 180 days). CONCLUSION: Patients with minimal amounts of recent onset myonecrosis but elevated risk as indicated by CK-MB and troponin, respectively, benefit most from invasive management. Determination of troponin levels yielded significant information regarding triage to an invasive strategy, particularly in CK-MB-negative patients.     

Antibody valence and induced signal transduction: the role of antibody valence in anti-CD3-induced signal transduction in isolated normal T cells

This report provides direct evidence that protein kinase C (PKC) is activated in isolated, rigorously accessory cell (AC)-depleted T cells when the T cell antigen recognition complex is stimulated by divalent anti-CD3 monoclonal antibody. Anti-CD3 monoclonal antibody-stimulated PKC activation alone does not, however, directly stimulate T cell proliferation in the absence of AC. A rise in cytosolic calcium is the second signal believed to be of paramount importance in T cell activation. While mitogenic concentrations of some divalent anti-CD3 antibodies do not cause a rise in cytosolic calcium, polyvalent anti-CD3 does evoke increased intracellular Ca2+ in rigorously AC-depleted resting human T cells.     

Ability of minor elevations of troponins I and T to predict benefit from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction: results from a randomized trial.

CONTEXT: Cardiac troponins I (cTnI) and T (cTnT) are useful for assessing prognosis in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). However, the use of cardiac troponins for predicting benefit of an invasive vs conservative strategy in this patient population is not clear. OBJECTIVE: To prospectively test whether an early invasive strategy provides greater benefit than a conservative strategy in acute coronary syndrome patients with elevated baseline troponin levels. DESIGN: Prospective, randomized trial conducted from December 1997 to June 2000. SETTING: One hundred sixty-nine community and tertiary care hospitals in 9 countries. PARTICIPANTS: A total of 2220 patients with acute coronary syndrome were enrolled. Baseline troponin level data were available for analysis in 1821, and 1780 completed the 6-month follow-up. INTERVENTIONS: Patients were randomly assigned to receive (1) an early invasive strategy of coronary angiography between 4 and 48 hours after randomization and revascularization when feasible based on coronary anatomy (n = 1114) or (2) a conservative strategy of medical treatment and, if stable, predischarge exercise tolerance testing (n = 1106). Conservative strategy patients underwent coronary angiography and revascularization only if they manifested recurrent ischemia at rest or on provocative testing. MAIN OUTCOME MEASURE: Composite end point of death, MI, or rehospitalization for acute coronary syndrome at 6 months. RESULTS: Patients with a cTnI level of 0.1 ng/mL or more (n = 1087) experienced a significant reduction in the primary end point with the invasive vs conservative strategy (15.3% vs 25.0%; odds ratio [OR], 0.54; 95% confidence interval [CI], 0.40-0.73). Patients with cTnI levels of less than 0.1 ng/mL had no detectable benefit from early invasive management (16.0% vs 12.4%; OR, 1.4; 95% CI, 0.89-2.05; P<.001 for interaction). The benefit of invasive vs conservative management through 30 days was evident even among patients with low-level (0.1-0.4 ng/mL) cTnI elevation (4.4% vs 16.5%; OR, 0.24; 95% CI, 0.08-0.69). Directionally similar results were observed with cTnT. CONCLUSION: In patients with clinically documented acute coronary syndrome who are treated with glycoprotein IIb/IIIa inhibitors, even small elevations in cTnI and cTnT identify high-risk patients who derive a large clinical benefit from an early invasive strategy.     

Succinylcholine-induced rhabdomyolysis in a healthy child

A case of Rhabdomyolysis occurred in a healthy boy 9 years of age after general anaesthesia. Succinylcholine, nitrous oxide and isoflurane were used for induction and maintenance of anaesthesia. Patient developed severe muscle pain, myoglobinuria, haemoglobinuria. Also creatinine phosphokinase was elevated up to 10,694 IU/L. Management was prompt and he was discharged home the third day in good condition. The injection of succinycholine may have precipitated rhabdomyolysis. This is a rare complication of succinylcholine without the disastrous outcome of renal failure, hyperkalaemia or cardiac arrest.     

The role of cytokines, CTLA-4 and costimulation in transplant tolerance and rejection.

T cell costimulation and cytokine production play an important role in generating the alloimmune responses that lead to allograft rejection. Recent data, however, provide evidence that costimulatory molecules, such as B7-1 and B7-2, and T cell activating cytokines, such as IFN-gamma and IL-2, also trigger negative feedback mechanisms in T lymphocytes which limit alloimmune responses. These feedback mechanisms are essential for the induction of long-term allograft acceptance and, in certain situations, transplantation tolerance.     

Vascularized Osteomyocutaneous Allografts Are Permissive to Tolerance by Induction‐Based Immunomodulatory Therapy

Vascularized composite allografts (VCAs) are unique among transplanted organs in that they are composed of multiple tissues with disparate antigenic and immunologic properties. As the predominant indications for VCAs are non‐life‐threatening conditions, there is an immediate need to develop tolerance induction strategies and to elucidate the mechanisms of VCA rejection and tolerance using VCA‐specific animal models. In this study, we explore the effects of in vitro induced donor antigen‐specific CD4^?CD8^? double negative (DN) Treg‐based therapy, in a fully MHC mismatched mouse VCA such as a vascularized osteomyocutaneous as compared to a non‐VCA such as a full thickness skin (FTS) transplantation model to elucidate the unique features of VCA rejection and tolerance. We demonstrate that combined therapy with antigen‐induced CD4 derived DN Tregs and a short course of anti‐lymphocyte serum, rapamycin and IL‐2/Fc fusion protein results in donor‐specific tolerance to VCA, but not FTS allografts. Macrochimerism was detected in VCA but not FTS allograft recipients up to >60 days after transplantation. Moreover, a significant increase of CD4⁺Foxp3⁺ Tregs was found in the peripheral blood of tolerant VCA recipients. These data suggest that VCA are permissive to tolerance induced by DN Treg‐based induction therapy.

     

Inhibition of dorsal column by nuclei stimulation of trigeminal afferents in decerebrate—decerebellate cats

In decerebrate—decerebellate cats, stimulation of trigeminal afferents inhibited neurons in dorsal column (DC) nuclei driven by activation of DC input and produced primary afferent depolarization in DC primary afferent terminals. This inhibition was most likely mediated by a trigeminal—brainstem—DC nuclear loop.     

Isolation of HTLV-II from a patient with chronic,progressive neurological disease clinically indistinguishable from HTLV-I-associated myelopathy/tropical spastic paraparesis

An increasing spectrum of diseases has been shown to be associated with the human T-cell lymphotropic virus type I (HTLV-I), most notably a chronic, progressive myelopathy termed HTLV-I-associated myelopathy/tropical spastic paraparesis and adult T-cell leukemia. HTLV-II is a close relative of HTLV-I and is structurally similar but molecularly distinct. This virus is endemic in Amerindian populations and a high seroprevalence rate has been observed in intravenous drug abusers. Here, for the first time, we have identified a patient with a chronic, progressive neurological disease clinically indistinguishable from HTLV-I-associated myelopathy/tropical spastic paraparesis from whom we have isolated and characterized HTLV-II in the absence of any other detectable human retrovirus. Antibodies to HTLV were deteced in both serum and cerebrospinal fluid, with typical HTLV-II banding patterns on Western blots. HTLV-II viral sequences were detected in high copy number from peripheral lymphocytes by polymerase chain reaction techniques, and cloning and sequencing of the virus revealed a 99.5% homology with prototype HTLV-II. These results serve to alert the medical community to the possibility that in addition to HTLV-I, HTLV-II may be associated with a neurological disorder.